• Adult men and women, age 18 or older.
• Previously seen at the Mayo Clinic Fibromyalgia and Chronic Fatigue Clinic (Rochester, MN) and diagnosed with fibromyalgia.
• Able to read and speak English.
• Must be willing and able to provide consent and participate in both portions of the study.

• Minors (under the age of 18).
• Patients not diagnosed with fibromyalgia.
• Patients who cannot provide consent or unwilling to participate in both portions of the study.

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

Eligibility last updated 4/27/23. Questions regarding updates should be directed to the study team contact.

• Women with diagnosis of any type of breast cancer.
• Women with breast cancer on unilateral or bilateral side.
• Women with surgical intervention for treatment of breast cancer.

• Previous shoulder injury or known shoulder limitation on affected side.

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

Eligibility last updated 5/18/23. Questions regarding updates should be directed to the study team contact.

• Adults over age 18 only.
• Normal controls will include individuals over the age of 18, who provide informed consent for gait analysis and do not have any medical condition affecting their gait and balance.
• Patients with Progressive Supranuclear Palsy (PSP):
  • Patients over the age of 35 meeting the 2017 Movement disorders society criteria for PSP will be recruited. To be able to participate in the gait analysis patients must be able to ambulate with or without a gait aid. Patients will be identified from the neurology clinic, where the PI commonly sees this condition.

• Subjects will be excluded if they do not have the symptoms necessary to fulfill inclusion criteria for PSP.
• Individuals with PSP at very advanced disease stage who are no longer ambulatory or are wheelchair bound excluded.
• Subjects with concurrent illnesses that could account for their gait and balance abnormality such as traumatic brain injury, encephalitis, strokes, amputation, injury or developmental syndromes will be excluded. Women that are pregnant or post-partum and breast-feeding will be excluded.

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

Eligibility last updated 5/10/23. Questions regarding updates should be directed to the study team contact.

- Willing to return to enrolling institution for study follow-up visit

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

- Willing to return to enrolling institution for study follow-up visit

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

- Willing to return to enrolling institution for study follow-up visit

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

• 18-21 years old.
• Fluent English speaker.
• Medically cleared to play ice hockey.

• Clinically documented hearing issues.
• In-ear hearing aid or cochlear implant.
• Implanted pacemaker or defibrillator.
• Metal or plastic implants in skull.
• lack of verbal fluency in the English language.
• History of seizures.
• Allergy to rubbing alcohol or EEG gel.

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

Eligibility last updated 5/17/23. Questions regarding updates should be directed to the study team contact.

• Provide oral consent for the study.
• Provide written consent for the procedure itself.
• 18-99 years of age.
• Undergoing outpatient, office-based laryngoscopy procedure

• Pregnancy.
• Body weight < 50 kg or > 110 kg.

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

Eligibility last updated 5/18/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•PAD Patients:

• Mild claudication to minor tissue loss (Rutherford 1-5).
• Resting or exercise ankle-brachial index < 0.9 or toe brachial index < 0.6.
• Age 35 or more.

Inclusion Criteria
•Healthy Volunteers:

• Age 35-90.

Exclusion Criteria
•PAD Patients and Healthy Volunteers: 

• Evidence of active infection.
• Chronic liver disease, end-stage renal disease (CKD 5), or chronic inflammatory disease.
• Poorly controlled diabetes (HbA1c > 8%).
• BMI < 18 or > 35.
• Recent other major surgery or illness within 30 days.
• Use of immunosuppresive medications or steroids.
• History of organ transplantation.
• Pregnancy, or plans to become pregnant, or lactating.

Exclusion Criteria - Healthy Volunteers:

• hsCRP > 2 mg/L.

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

Eligibility last updated 5/19/23. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Histological confirmation of prostate cancer.
• Planned definitve dose radiotherapy to the prostate.
• ECOG Performance Status (PS) 0-2.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Provide written informed consent.

• Planned delivery of radiotherapy to pelvic lymph nodes.
• Planned brachytherapy treatment of the prostate.
• Significant urinary incontinence that precludes standard bladder filling.
• Evidence of direct bladder extension or bladder wall metastases from prostate cancer.
• Use of indwelling or intermittent urinary catheterization at baseline.
• Prior pelvic radiotherapy such that any portion of the prostate received > 5 Gy.
• Provide written informed consent.

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

Eligibility last updated 6/7/23. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Histological confirmation of prostate cancer.
• Planned definitve dose radiotherapy to the prostate.
• ECOG Performance Status (PS) 0-2.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Provide written informed consent.

• Planned delivery of radiotherapy to pelvic lymph nodes.
• Planned brachytherapy treatment of the prostate.
• Significant urinary incontinence that precludes standard bladder filling.
• Evidence of direct bladder extension or bladder wall metastases from prostate cancer.
• Use of indwelling or intermittent urinary catheterization at baseline.
• Prior pelvic radiotherapy such that any portion of the prostate received > 5 Gy.
• Provide written informed consent.

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

Eligibility last updated 6/7/23. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Histological confirmation of prostate cancer.
• Planned definitve dose radiotherapy to the prostate.
• ECOG Performance Status (PS) 0-2.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Provide written informed consent.

• Planned delivery of radiotherapy to pelvic lymph nodes.
• Planned brachytherapy treatment of the prostate.
• Significant urinary incontinence that precludes standard bladder filling.
• Evidence of direct bladder extension or bladder wall metastases from prostate cancer.
• Use of indwelling or intermittent urinary catheterization at baseline.
• Prior pelvic radiotherapy such that any portion of the prostate received > 5 Gy.
• Provide written informed consent.

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

Eligibility last updated 6/7/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria:

• Patients that come for facial plastic/reconstructive surgery involving facial fat injection or other facial reconstruction surgery.

Exclusion Criteria:

• Patients treated with immunotherapy.
• Patients treated with chemotherapy/radiation therapy.
• Smokers.
• Patients with immuno-suppressed or compromised disease.
• Patients with diabetes.

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

Eligibility last updated 6/7/23. Questions regarding updates should be directed to the study team contact.

• 18 years of age or older at the time of 1st interview.
• English-speaking.
• Self-reported non-cisgender.

• < 18 years of age.

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

Eligibility last updated 6/29/23. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• A clinician-diagnosed Type 1, Type 2, or gestational diabetes.
• Receiving diabetes care by any clinician at the Division of Endocrinology.
• Use any treatment to achieve glycemic control.
• Users of any form of digital device or software for diabetes management.
• Ability to read, speak, and understand English.
• Access to telephone/videoconferencing technology for interviews or ability to meet study staff in person for an interview.
• Ability and willingness to participate in all study related surveys and questionnaires.

• Patients for whom caregivers are the main users of digital tools in support of the patient’s care.
• Participants who, in the opinion of the research staff, exhibit clinically significant cognitive or memory (e.g., the participant has trouble holding a conversation, or the participant exhibits signs of disorientation) or sensorial impairment that limits the participant’s ability to give informed consent.

Eligibility last updated 7/26/23. Questions regarding updates should be directed to the study team contact.

• 18 years of age or older.
• Plan to initiate treatment with either bi-specific antibody or CAR-T therapy either as standard of care or through clinical trial.
• Capacity to understand the protocol and its requirements, risks, and discomforts.
• Capacity and willingness to sign informed consent.

• Pregnancy or lactation (for females).
• Inability on the of the part of the patient to understand the informed consent or be compliant with the protocol.
• Any condition, which in the opinion of the patient's treating physician, or the provider performing the biopsy procedure, would make participation in this protocol unreasonably hazardous for the patient (including a history of a serious or life-threatening allergic reaction to such local ansesthetics as lidocaine or xylocaine).

• Patients already scheduled for a percutaneous MR guided procedure

• Pregnant Women

Casual Observers

• 18 years or older.
• Normal eye movements and binocular vision (with or without correction).
• Ability to speak and read English.

• Age less than 18 years old.
• Eye movement limitations such as spontaneous nystagmus or strabismus.
• Monocular vision.
• Psychiatric condition as studies have shown that individuals with psychiatric conditions (particularly schizophrenia and autism spectrum disorder) result in altered visual attention to the face. 
• If casual observers respond yes to these questions they will be thanked for their interest and excluded from the study
•  

Patients

• Age 18-80 years.
• Recipient of kidney transplantation 4 or more years.
• Competent and able to provide written informed consent.
• Ability to comply with protocol.

• Patients have clinically significant medical conditions within the prior 6 months before: e.g. myocardial infarction, congestive heart failure, or stroke, that would, in the opinion of the investigators, compromise the safety of the patient.
• Severe chronic liver, heart, or lung disease.
• Undergoing acute rejection.
• Contra-indication to biopsy; bleeding disorders.
• Chronic infection.
• Any active malignancy and undergoing therapy.
• Kidney or ureteric stone.
• Unable to give valid informed consent.
• Known pregnancy or intent to conceive during the study period.
• Pacemaker, implantable defibrillator, magnetically active metal fragments, claustrophobia, or other contraindication to MRI.
• Federal medical center inmates.

Eligibility last updated 9/13/22. Questions regarding updates should be directed to the study team contact.

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

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

PRIOR TO STEP 1 REGISTRATION INCLUSION CRITERIA

• Pathologically (histologically or cytologically) confirmed diagnosis of epithelioid or biphasic malignant pleural mesothelioma (MPM) within 90 days prior to Step 1 Registration -Imaging proof of clinical stage (American Joint Committee on Cancer [AJCC] 8th edition) I-IIIA MPM by PET/CT within 42 days prior to Step 1 Registration.
• MPM is amenable to resection by P/D as determined by a thoracic surgeon within 42 days prior to Step 1 Registration.
• History/physical examination within 42 days prior to Step 1 Registration.
• Karnofsky performance status ≥ 80 within 42 days prior to Step 1 Registration.
• Pulmonary function tests within 42 days prior to Step 1 Registration:
  • ≥ 40% predicted post-forced expiratory volume in 1 second (FEV1);
  • ≥ 40% predicted post-operative diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin [Hgb]).
• Leukocytes ≥ 3000 cells/mm^3 (within 30 days prior to Step 1 Registration).
• Absolute neutrophil count ≥ 1500 cells/mm^3 (within 30 days prior to Step 1 Registration).
• Platelets ≥ 100,000 cells/mm^3 (within 30 days prior to Step 1 Registration)..
• Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) (within 30 days prior to Step 1 Registration).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine a minotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3.0 X ULN (within 30 days prior to Step 1 Registration).
• Glomerular filtration rate (GFR): ≥ 50 mL/min/1.73 m^2 (must be calculated using estimated creatinine clearance [CrCl] by the Cockcroft-Gault [C-G] equation [Nephron 1976;16:31-41]) (within 30 days prior to Step 1 Registration).
• Negative serum pregnancy test within 14 days of Step 1 Registration for pre-menopausal women of childbearing potential.
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.
• EORTC QLQ-C30 and QLQ-LC13 within 42 days prior to Step 1 Registration.

PRIOR TO STEP 2 RANDOMIZATION INCLUSION CRITERIA

• Patients must have received at least 2 cycles of pemetrexed/platinum chemotherapy and undergone a pleurectomy/decortication with the goal of macroscopic complete resection following step 1 Registration.
• Karnofsky performance status ≥ 70 within 30 days prior to Step 2 Randomization.
• History/physical examination within 30 days prior to Step 2 Randomization.
• EORTC QLQ-C30 and QLQ-LC13 within 30 days prior to Step 2 Randomization.

PRIOR TO STEP 1 REGISTRATION EXCLUSION CRITERIA

• Pregnant or lactating women, or sexually active men or women not using effective contraception (risk for fetal defects from teratogenic chemotherapy and radiation therapy) within 14 days prior to Step 1 Registration
• Diagnosis of sarcomatoid mesothelioma.
• Severe, active co-morbidity defined as follows:
  • New York Heart Association (NYHA) class III or IV heart failure;
  • Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are allowed;
  • Unstable angina requiring hospitalization and/or transmural myocardial infarction within the last 3 months;
  • Interstitial lung disease;
  • Hemodialysis or peritoneal dialysis;
  • Concurrent active malignancy (with the exception of current or prior non-melanomatous skin cancer or low-grade malignancies followed observantly for which treatment has not or does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen).
• If evidence of disease < 3 years, institution must consult with the principal investigator, Andreas Rimner, Doctor of Medicine (MD)
• Hepatic impairment defined by ChildPugh class (ChildPugh class B & C);
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated.
  • Note: HBV viral testing is not required for eligibility for this protocol.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured.
• For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 30 days prior to registration.
• Active tuberculosis.
• Patients on immunosuppressive therapy, for example history of organ or bone marrow transplant or chronic lymphocytic leukemia (CLL).
• CD4 count < 200 cells/microliter.
  • Note that patients who are human immunodeficiency virus (HIV) positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count  200 cells/microliter within 30 days prior to registration.
  • Note also that HIV testing is not required for eligibility for this protocol.
• Prior nephrectomy on the contralateral side of MPM.
• Ipsilateral thoracic electronic implant; e.g., pacemaker, defibrillator, unless switched to the contralateral side prior to initiation of radiation therapy (RT).
• Prior thoracic radiation therapy (patients with prior thoracic RT cannot be planned to 50-60 Gy without exceeding normal tissue constraints).

PRIOR TO STEP 2 RANDOMIZATION EXCLUSION CRITERIA

• Progressive disease.
• Supplemental oxygen use.
• Third space fluid that cannot be controlled by drainage or insufficient lung expansion after P/D (this prevents targeting the pleura without exceeding normal tissue constraints).
• Prior intrapleural therapy (i.e., intrapleural chemotherapy, photodynamic therapy); pleurodesis is permitted.
• Bulky residual disease in the major fissure preventing pleural IMRT.
• Patients who have undergone extrapleural pneumonectomy.
• Patients with active infection that requires systemic I.V. antibiotics, antiviral, or antifungal treatments.

• Participant must be ≥ 34 weeks of corrected gestational age (CGA), < 46 weeks of CGA, and < 28 days of postnatal age (PNA), at the time of signing the informed consent.
• Participants who have confirmation on video-EEG of ≥ 2 minutes of cumulative ENS or ≥ 3 identifiable ENS prior to entering the Treatment Period (ENS is defined as a seizure lasting for at least 10 seconds on video-EEG), despite receiving previous AED treatment for the treatment of electroencephalographic seizures. The occurrence of ENS during an up to 1-hour period must be confirmed by the local video-EEG reader prior to randomized study drug administration. Video-EEG recording can be shortened per clinical need (e.g., if status epilepticus is detected). If possible, an attempt should be made to record at least 30 minutes of Baseline video-EEG.
• Participants must have received either PB, LEV, or MDZ (in any combination) before entering the study.
• Participants with or without concomitant hypothermia treatment.
• Participant weighs at least 2.3kg at the time of enrollment.
• An Independent Ethics Committee (IEC)-approved written ICF is signed and dated by the participant’s parent(s) or legal representative(s).

• Participant with seizures responding to correction of metabolic disturbances (hypoglycemia, hypomagnesemia, or hypocalcemia) or with seizures for which a targeted, known treatment is available.
• Participant has seizures related to prenatal maternal drug use or drug withdrawal.
• Participant has known severe disturbance of hemostasis, as assessed by the investigator.
• Participant has a poor prognosis for survival, as judged by the investigator.
• Participant has a medical condition that could be expected, in the opinion of the investigator, to interfere with study medication absorption, distribution, metabolism, or excretion.
• Participant has a clinically relevant ECG abnormality, in the opinion of the investigator (eg, second or third degree heart block at rest or a corrected QT interval [QTc] ≥ 450ms).
• Participant has a hemodynamically significant congenital heart disease.
• Participant has any clinically relevant cardiac arrhythmia.
• If participant is in the first 24 hours of life, urine output is < 1 mL/kg/hour.  If older than 24 hours, participant urine output is < 1 mL/kg/hour or serum creatinine is > 1.7 mg/dL.
• Participant receiving treatment with PHT, LDC, or other sodium channel blockers at any time.
• Participant requires extracorporeal membrane oxygenation.
• Participant requires or is expected to require phototherapy or exchange transfusion due to elevated bilirubin.
• Participant has 2 x upper limit of normal (ULN) of any of the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), with the following exception:
  • For participants with perinatal asphyxia, elevation of AST, ALT, or ALP 2mg/dL.

Eligibility last updated 4/14/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Documented CD20+ mature B-cell neoplasm according to WHO classification (Swerdlow et al., 2016) as one of the following:
  • Diffuse large B-cell lymphoma NOS including:
  • Transformed lymphoma;
  • Richter’s transformation;
  • Germinal center B-cell type;
  • Activated B-cell type;
  • High-grade B-cell lymphoma (HGBCL), NOS);
  • Primary mediastinal (thymic) large B-cell lymphoma.
• Patients with “double-hit” or “triple-hit” DLBCL (technically as HGBCL, with MYC and BCL2 and/or BCL6 rearrangements).
• Follicular lymphoma 3B.
• T-cell/histiocyte-rich large B cell lymphoma.
• Large B-cell lymphoma with IRF4 rearrangement.
• Primary cutaneous DLBCL, leg type.
• EBV positive DLBCL, NOS.
• DLBCL associated with chronic inflammation.
• Intravascular large B-cell lymphoma.
• ALK positive large B-cell lymphoma.
  • Relapsed, progressive and/or refractory disease (Cheson et al., 2007) following treatment with an anti-CD20 monoclonal antibody (e.g., rituximab)  in combination with chemotherapy
    • Measurable disease as defined below: 
    • Fluorodeoxyglucose (FDG)-avid lymphomas: Measurable disease with computerized tomography (CT) (or magnetic resonance imaging [MRI]) scan with involvement of 2 or more clearly demarcated lesions/nodes with a long axis > 1.5 cm and short axis > 1.0 cm (or 1 clearly demarcated lesion/node with a long axis > 2.0 cm and short axis ≥ 1.0 cm) AND FDG positron emission tomography (PET) scan that demonstrates positive lesion(s) compatible with CT (or MRI) defined anatomical tumor sites.
• FDG-nonavid lymphomas: Measurable disease with CT (or MRI) scan with involvement of 2 or more clearly demarcated lesions/nodes with a long axis > 1.5 cm and short axis > 1.0 cm or 1 clearly demarcated lesion/node with a long axis > 2.0 cm and short axis ≥ 1.0 cm.
• ECOG Performance Status (PS) 0 or 1.
• ≥ 4 weeks from last dose of anti-CD20 targeting therapy.      
• ≥ 12 weeks post CAR T-cell therapy.
• Resolution of all adverse events due to prior therapy to ≤ Grade 1 or baseline. NOTE: Patients with ≤ Grade 2 neuropathy may be eligible. Patients with endocrine-related AEs Grade ≤ 2 requiring treatment or hormone replacement may be eligible.  investigator
• If receiving glucocorticoid treatment at screening, treatment must be tapered down and administered with a maximum of 10 mg daily in the last 14 days prior to registration.
• The following laboratory values obtained ≤ 7 days prior to registration:
• • •  
  • Absolute neutrophil count (ANC) ≥ 500/mm^3; growth factor support allowed in case of bone marrow involvement;
  • Absolute lymphocyte count  ≥200/mm^3;
  • Platelet count ≥75,000/mm3;
  • Hemoglobin ≥ 8.0 g/dL;
  • INR or PTT/aPTT ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants;
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN), unless due to Gilbert’s disease (direct bili ≤ ULN);
  • Aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) ≤ 2.5 x ULN;
  • Calculated creatinine clearance ≥30 mL/min using the Cockcroft-Gault formula below:
  • Cockcroft-Gault Equation:
    • Creatinine clearance for males =    (140
      •age) (weight in kg) / (72) (serum creatinine in mg/dL);
    • Creatinine clearance for females = (140
      •age) (weight in kg) (0.85) / (72)(serum creatinine in mg/dL).
• Provide informed written consent.
• Negative pregnancy test done ≤ 3 days prior to registration, for persons of childbearing potential only.
• Female of childbearing must agree to use a highly effective method of contraception during the treatment and for 120 days after the last dose of study treatment.
• Male participants with female partners of childbearing potential must agree to refrain from donating sperm and one of the conception methods as described in Appendix V during the treatment and for 120 days after last dose study treatment.
• Willing to return to the enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Willing to provide mandatory tissue and blood samples for correlative research purposes.

Exclusion Criteria:

• Primary ce ntral nervous system (CNS) lymphoma or known CNS involvement by lymphoma at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) and, if clinically indicated, by lu
• Known past or current malignancy other than inclusion diagnosis, except for:
  22.  
  • Cervical carcinoma of Stage 1B or less;
  • Non-invasive basal cell or squamous cell skin carcinoma;
  • Non-invasive, superficial bladder cancer;
  • Prostate cancer with a current PSA level < 0.1 ng/mL;
  • Any curable cancer with a complete response (CR) of > 2 years duration.
• Received < 2 prior systemic anti-cancer therapy including investigational agents ≤ 4 weeks or ≤5 half-lives, whichever is shorter, prior to registration.
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137) ≤ 4 weeks  prior to registration.
• Known clinically significant cardiac disease, including:
• • Onset of unstable angina pectoris within 6 months of signing ICF;
  • Acute myocardial infarction within 6 months of signing ICF;
  • Congestive heart failure (grade III or IV as classified by the New York Heart Association and/or known decrease ejection fraction of < 45%).
• Chronic ongoing infectious diseases (except hepatitis B or hepatitis C) requiring treatment (excluding prophylactic treatment) at the time of enrollment or ≤ the previous 2 weeks.
• Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy or primary immunodeficiency disorder. Low-dose steroids (≤10 mg daily of prednisone equivalent) is allowed.
• Seizure disorder requiring therapy (such as steroids or anti-epileptics).
• Autologous HSCT ≤ 100 days prior or any prior allogeneic HSCT or solid organ transplantation.
• Known human immunodeficiency virus (HIV) infection.
• Exposed to live or live attenuated vaccine ≤ 4 weeks prior to registration.
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential who are unwilling to employ adequate contraception.
• Patient has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Uncontrolled intercurrent illness including, but not limited to:
  • ongoing or active infection;
  • uncontrolled infection requiring ongoing antibiotics;
  • symptomatic congestive heart failure;
  • unstable angina pectoris;
  • cardiac arrhythmia;
  • or psychiatric illness/social situations that would limit compliance with study requirements;
  • known substance abuse disorder.
• Known hypersensitivity to pembrolizumab.
• Major surgery other than diagnostic surgery ≤ 4 weeks prior to registration.
• Prior radiation therapy ≤ 2 weeks prior to registration or who has not recovered from all  radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  • Note:  A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
• Active autoimmune disease such as Crohn’s disease, rheumatoid arthritis, Sjogren’s disease, systemic lupus erythematosus, or similar conditions requiring systemic treatment ≤ the past 3 months or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past.
• EXCEPTIONS:
  • Vitiligo or resolved childhood asthma/atopy;
  • Intermittent use of bronchodilators or local steroid injections;
  • Hypothyroidism stable on hormone replacement;
  • Diabetes stable with current management;
  • History of positive Coombs test but no evidence of hemolysis;
  • Psoriasis not requiring systemic treatment;
  • Conditions not expected to recur in the absence of an external trigger.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection.
• Prior anti CD47 therapy.
• Active use of anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis.
• There will be no restriction for daily aspirin < 81mg daily.
• Co-morbid systemic illnesses  or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

Eligibility last updated 6/24/22. Questions regarding updates should be directed to the study team contact.

PRE-REGISTRATION

• Histologically confirmed glioblastoma (World Health Organization [WHO] grade IV) presenting at first or second recurrence including secondary glioblastoma.
• Presence of measurable disease, as defined by a bidimensionally measurable lesion on magnetic resonance imaging (MRI) with a minimum diameter of 10 mm in both dimensions, prior to resection or biopsy of recurrent tumor.
• Tissue available from surgical resection or biopsy of recurrent tumor ≤ 14 days prior to pre-registration, or planned surgery or biopsy of recurrent tumor ≤ 14 days after pre-registration.
• Does not require > 4 mg dexamethasone beyond the perioperative period defined as the time ≤ 2 weeks after surgical procedure.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Able to undergo brain MRI with contrast.
• Absolute neutrophil count ≥ 1500/mm^3.
• Platelet count ≥ 100,000/mm^3.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
• If Gilbert syndrome, then total bilirubin ≤  3 x ULN.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN.
• Creatinine ≤ 1.5 x ULN OR creatinine clearance (CrCl) ≥ 50 mL/min (if using the Cockcroft-Gault formula).

REGISTRATION

• Tissue obtained from biopsy or resection at first or second recurrence exhibits TMB ≥ 20 on FoundationOne CDx testing.

• No active autoimmune disease or history of autoimmune disease.
• These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease.
• Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
• Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• No prior treatment with checkpoint blockade therapies (anti-CTLA4, anti-PD1/PD-L1) or bevacizumab.

• Histologically or cytologically confirmed metastatic PDAC
• Has received 1 prior gemcitabine-based chemotherapy as first line therapy for metastatic disease. Progression after completion of neoadjuvant or adjuvant therapy of < 6 months in duration is considered 1 line of therapy for metastatic disease
• Has measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Must be willing and able to undergo a tissue biopsy at screening; participants who, in the opinion of the investigator, do not have tissue that is accessible for biopsy are excepted from this criterion
• Women of childbearing potential: (defined as not post-menopausal for 12 months or no previous surgical sterilization) and fertile men must agree to use adequate contraception for the duration of study participation and for 4 months after the last dose of nal-IRI. Male subjects must agree to refrain from sperm donation during the study and for 4 months after the last dose of nal-IRI
• Ability to understand and the willingness to sign a written informed consent document. Signed informed consent form must be obtained prior to initiation of study evaluations and/or activities
• International Normalized Ratio (INR) < 1.5 unless on warfarin
• Participants with prior malignancy and who were treated with no evidence of active disease more than 2 years from initial diagnosis are eligible
• Age ≥ 18 years
• Participants must have adequate organ and bone marrow function

• Prior treatment with irinotecan, nal-IRI, or investigational PLK1 inhibitor
• Uncontrolled intercurrent illness including symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, and myocardial infarction within 3 months of initiation of therapy
• History of interstitial pneumonitis or interstitial lung disease
• Participants with microsatellite instability-high (MSI-H) tumors with no prior immune checkpoint inhibitor exposure
• Pregnancy or lactation
• Participant has active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
• QT interval with Fridericia's correction (QTcF) > 470 milliseconds. The QTcF should be calculated as the arithmetic mean of the QTcF on triplicate electrocardiograms (ECGs). In the case of potentially correctible causes of QT prolongation, (eg, medications, hypokalemia), the triplicate ECG may be repeated once during Screening and that result may be used to determine eligibility
• Planned concomitant use of medications known to prolong the QT/QTc interval
• Participant has undergone major surgical resection within 4 weeks prior to enrollment
• Participant received radiotherapy, surgery, chemotherapy, or an investigational therapy within 2 weeks prior to study entry
• Participant has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the participant to receive an experimental research drugs
• Serious psychiatric or medical conditions that could interfere with treatment
• Major bleeding in the last 4 weeks
• More than 1 prior chemotherapy regimen administered in the metastatic setting
• Unable or unwilling to swallow oral medication -Use of strong CYP3A4 or UGT1A1 inhibitors or strong CYP3A4 inducers. Participants currently receiving these agents who are able to switch to alternate therapy are not excluded. Inhibitors should be stopped at least one week prior to the first dose of protocol therapy and inducers should be stopped at least two weeks prior to initiation of protocol therapy.

• Having spontaneous coronary artery dissection.
• Sex and age-matched control subjects, 18 years of age and older.

• Individuals under 18 years of age.

• Has Mayo Clinic or other medical health system ID, or another unique identifier.
• Able to provide informed consent.
• Individual must have evidence of a genetic disorder as determined by a provider or genetic counselor with causative or likely causative genetic variants identified by molecular testing.
• Genetic variants must be hypothesized to be targetable using antisense oligonucleotide drugs (such as: knockdown gain of function alterations, increase protein production for reduced function alterations, or modulate mRNA splicing to correct abnormal splicing, promote normal splicing, or return reading frame to an out-of-frame transcript to restore function, etc.) based on current acceptable understanding of ASO mechanisms of action and tissue/organ targeting efficiency.
• Biological family member of an enrolled individual.
• Would be able to travel to a Mayo Clinic site for ongoing treatment should a therapeutic be developed.
• Treatment at the individual’s current disease state would likely provide benefit based on current clinical data and understanding of the progression of the disease.

 Exclusion Criteria

• Individuals who have situations that would limit compliance with the study requirements.
• Institutionalized (i.e., Federal Medical Prison).

• Men or women.
• 22 to 80 years old.
• Unruptured cerebral aneurysm scheduled for flow diverter treatment at St. Marys Hospital.
• Patients who may require pre-treatment with Lorazepam/Ativan prior to MRI scanning provided they have an adult accompanying and driving for them after the scan is completed.

• Any prior stent or coil treatments.
• IVC filter removal in last twelve months.
• Unable to have MRI imaging exams due to coil, filter, stent or wire or an implanted device such as IVC filter, pacemaker, nerve stimulator, medication pump or other on body injector delivery system/sensor or tattoo ink that if it contained metal could heat up and/or or generate image artifact.  
• Not able to return for follow-up MRI imaging and blood collection in three to twelve months post flow diversion (FD) treatment.
• Pregnant or breast-feeding females.
• Cancer diagnosis and having had (last twelve months) or currently undergoing radiation and/or chemotherapy treatments.
• Persons lacking capacity.
• Prisoner.

Eligibility last updated 8/30/21. Questions regarding updates should be directed to the study team contact.

• Age 50 years or older.
• English speaking.
• Admitted to the intensive care unit (medical or surgical).
• Expected mechanical ventilator support for ≥ 48 hours.
• Consentable through a legally authorized representative.
• Have access to a telephone (after discharge).

• History of dementing illnesses and other neurodegenerative diseases such as Alzheimer’s disease or vascular dementia.
• Psychiatric illness which is not well controlled.
• Alcohol withdrawal symptoms/concern for withdrawal.
• Suspected or confirmed drug intoxication/overdose.
• Traumatic brain injury, ischemic or hemorrhagic cerebrovascular accident, or undergoing neurosurgery.
• Uncorrected hearing or vision impairment including legal blindness.
• Incarcerated at the time of study enrollment.
• Enrolled in another clinical trial which does not permit co-enrollment.
• Any medical condition precluding safe use of headphones such as:  skin breakdown, burns, facial or skull fractures.
• COVID-19 positive test.

• Subjects with chronic kidney disease (estimated glomerular filtration rate < 60).
• Recruitment will primarily focus on patients with end stage renal disease who are being considered for renal transplantation or initiation of hemodialysis.
• Minorities will be included.

• Individuals < 18 years of age.
• Subjects not diagnosed with chronic kidney disease.

Eligibility last updated 8/18/21. Questions regarding updates should be directed to the study team contact.