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Inclusion Criteria: Patients are eligible to be enrolled for randomization in the study only if they meet all of the following criteria: 1. Written informed consent prior to any specific study procedures, showing patient willingness to comply with all study procedures. 2. Histologically or cytologically documented locally recurrent inoperable or metastatic breast cancer with HER2+ status based on local laboratory determination, preferably on the most recent available FFPE tumor sample, and according to American Society of ClinicalOncology (ASCO)/College of American Pathologists (CAP) international guidelines valid at the time of the assay. In case of discordance in HER2+ status in different biopsies, we will consider the result from the most recent biopsy one will be used. 3. Documented HR status based on local laboratory, preferably on the most recent available FFPE tumor sample, and according to ASCO/CAP international guidelines valid at the time of the assay. In case of discordance in HR status in different biopsies, the result from the most recent biopsy will be used. HR+ will be defined as ≥1% positive cells by immunohistochemistry for Estrogen Receptor (ER) and/or Progesterone Receptor (PgR). HR- will be defined as \<1% positive cells by immunohistochemistry for both ER and PgR. Considering that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive, for the purpose of this study, patients with ER and PgR expression between 1 and 10% (considered to be HR low by the most recent ASCO/CAP guidelines) will be eligible for inclusion in the HR- cohort. 4. Patients with a PIK3CA tumor mutation at central laboratory determination, preferably on the most recent available FFPE tumor sample. 5. At least 1 but no more than 5 prior lines of anti-HER2 based therapy for metastatic breast cancer (MBC). Maintenance therapy will not count as an additional line of therapy. 6. At least 1 prior line of trastuzumab in the metastatic setting, or in the (neo)adjuvant setting (provided the patient relapsed while on therapy or within 6 months after completing adjuvant trastuzumab). 7. Female or male patient is at least 18 years of age. 8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. 9. Patients can be either males or premenopausal/perimenopausal or postmenopausal females. In the HR+ cohort, males and females who are not post-menopausal must have been on a gonadotropin-releasing hormone (GnRH) agonist (e.g. goserelin or leuprorelin) for at least 28 days prior to starting study treatment. Premenopausal status is defined as either: * Last menstrual period occurred within the last 12 months, or * If on tamoxifen: last menstrual period occurred within the past 14 days, plasma estradiol is ≥ 10 pg/mL and follicle-stimulating hormone (FSH) ≤ 40 IU/l or in the premenopausal range, according to local laboratory definition, or * In case of therapy induced amenorrhea: plasma estradiol is ≥ 10 pg/mL and FSH ≤ 40 IU/l or in the premenopausal range, according to local laboratory definition. Postmenopausal status is defined as either: \- Natural (spontaneous) amenorrhea lasting more than 12 months and either age from49 to 59 years and/or history of vasomotor symptoms (e.g., hot flush) in the absence of other medical justification, or Levels of plasma estradiol ≤ 20 pg/mL and follicle-stimulating hormone (FSH) ≥ 40 IU/l or in the postmenopausal range, according to local laboratory definition, or Surgical bilateral oophorectomy. Perimenopausal status is defined as neither premenopausal nor postmenopausal. 10. Measurable disease or at least one evaluable bone lesion, lytic or mixed (lytic+blastic), which has not been previously irradiated and is assessable by computer tomography (CT)/magnetic resonance imaging (MRI) in the absence of measurable disease according to RECIST 1.1 criteria. 11. Life expectancy ≥ 12 weeks. 12. Adequate organ and marrow function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,500/mm3 (1.5x109/L). * Platelets ≥ 100,000/mm3 (100x109/L). * Hemoglobin ≥ 9g/dL (90g/L). * Calcium (corrected for serum albumin) and magnesium within normal limits or ≤ grade 1 according to NCI-CTCAE version 5.0 if judged clinically not significant by the investigator. * Creatinine \<1.5 x upper limit of normal (ULN) or creatinine Clearance ≥ 35 mL/min using Cockcroft-Gault formula (if creatinine is ≥1.5 ULN). * Total bilirubin \< 2 x ULN (any elevated bilirubin should be asymptomatic at enrollment) except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN. * Potassium within normal limits, or corrected with supplements. * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN. If patient has liver metastasis, AST and ALT ≤ 5.0 x ULN (elevated AST or AST values must be stable for 2 weeks, without evidence of biliary obstruction by imaging). * Fasting serum amylase ≤ 2.0 x ULN. * Fasting serum lipase ≤ ULN. * Fasting plasma glucose (FPG) \< 140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) \< 6.5%. 13. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI-CTCAE version 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion). 14. Adequate cardiac function as defined by left ventricular ejection fraction (LVEF) of ≥ 50% measured by echocardiography or multi-gated acquisition (MUGA) scans. Exclusion Criteria: Patients will be excluded from the study if they meet any of the following criteria: 1. Have received more than 5 previous lines of anti-HER2 based therapy for MBC, or prior fulvestrant. 2. Symptomatic visceral disease or any disease burden that makes the patient ineligible for experimental therapy per the investigator's best judgment. 3. Symptomatic central nervous system (CNS) metastases. However, patients with CNS metastases who have been adequately treated, are asymptomatic and do not require corticosteroid or anti-epileptic medication are eligible. 4. Presence of leptomeningeal carcinomatosis. 5. Other invasive malignancy (different from the current breast cancer) at the time of enrollment or previous diagnosis of a completely removed malignancy within 3 years prior to randomization except for adequately treated (including complete surgical removal) of International Federation of Gynecology and Obstetrics (FIGO) stage I grade 1 endometrial cancer, basal or squamous cell carcinoma of the skin, thyroid cancer limited to thyroid gland, in situ carcinoma of the cervix, and grade 1-2 early stage bladder cancer defined as T1 or less, without nodal involvement (N0). 6. Patients with an established diagnosis of diabetes mellitus type I or not controlled type II (FPG ≥ 140 mg/dL \[7.7 mmol/L\] or HbA1c ≥ 6.5%), or history of gestational diabetes (as per American College of Obstetricians and Gynecologists (ACOG) guidelines) or documented steroid-induced diabetes mellitus. 7. Prior treatment with any mTOR, AKT or PI3K inhibitor. 8. Patients treated within the last 7 days prior to treatment initiation with: * Drugs that are strong inducers of CYP3A4. * Drugs that are inhibitors of Breast Cancer Resistance Protein (BCRP). 9. Patients who received before randomization: * Any investigational agent within 4 weeks. * Chemotherapy within a period of time that is shorter than the cycle duration used for that treatment (e.g. \< 3 weeks for fluorouracil, doxorubicine, epirubicin or \< 1 week for weekly chemotherapy). * Biologic therapy (e.g., antibodies, other than trastuzumab which is permitted): within 4 weeks prior to starting study treatment. * Endocrine therapy: tamoxifen or aromatase inhibitor (AI) within 2 weeks prior to starting study treatment. * Corticosteroids within 2 weeks prior t

Inclusion Criteria: * Average office BP ≥140/90 mmHg at screening visit despite taking stables doses of antihypertensive medications for at least 4 weeks prior to consent * Documented daytime ABP ≥135/85 mmHg following 4 week run-in/standardization period on antihypertensive medication regimen Exclusion Criteria: * Renal artery anatomy ineligible for treatment * Secondary hypertension not including sleep apnea * Type I diabetes mellitus or uncontrolled Type II diabetes (defined as plasma HbA1c ≥9.0%) * eGFR \<40 * Brachial circumference ≥42 cm * Any history of cerebrovascular event or severe cardiovascular event within 3 months prior to consent * Documented repeat (\>1) hospitalization for hypertensive crisis within 3 months prior to consent * Documented confirmed episode(s) of unstable angina within 3 months prior to consent * Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea * Primary pulmonary hypertension * Night shift workers * Pregnant, nursing or planning to become pregnant

Inclusion Criteria: * Women with histologically confirmed luminal (ER+ve and/or progesterone \[PgR\]+ve \>= 1%) operable IBC (cT1-2, cN0-1, Mx) candidate to elective surgery and not to neo-adjuvant treatment. Women with larger tumors who refuse neo-adjuvant chemotherapy before surgery can also be eligible. Luminal HER2+ve (cT1, cN0) IBC and DCIS are also eligible * Age \>= 18 years * Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%) * Leukocytes \>= 3,000/microliter * Absolute neutrophil count \>= 1,500/microliter * Platelets \>= 100,000/microliter * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal * Creatinine within normal institutional limits * Creatinine clearance estimated with Cockcroft-Gault formula \> 45 mL/min * Female participants of child-bearing potential must agree to use contraception such as barrier method of birth control or abstinence, prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she has to inform her study physician immediately. The effects of metformin hydrochloride extended release on the developing human fetus at the recommended therapeutic dose are unknown * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Body mass index (BMI) \< 18.5 Kg/m\^2 * Previous treatment for breast cancer including chemotherapy and endocrine therapy within the last 12 months * Women who are planned to receive neoadjuvant therapy * Triple negative breast cancer (BC) * Patients with a history of cancer within the last year. NOTE: Non melanoma skin cancer is allowed. * Documented history of symptomatic hypoglycemia * Diabetic patients or participants with fasting glucose level \>= 126 mg/dL * Known hypersensitivity or intolerance to metformin hydrochloride extended release * Participants should not be receiving any other investigational agents * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * History of lactic acidosis * Liver dysfunction including chronic active hepatitis and cirrhosis not compensated * History of vitamin B12 deficiency or megaloblastic anemia * Chronic use of large doses of diuretics (e.g., \> 80 mg furosemide) * Current use of oral hormonal contraceptives or female hormones in the last four weeks or 5 half-lives, excluding vaginal creams and intrauterine devices (IUDs) * Concomitant use of topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) * Pregnant or lactating women. Pregnant women are excluded from this study because even though published data from post-marketing studies have not reported a clear association between metformin hydrochloride extended release and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin hydrochloride extended release was used during pregnancy, these studies cannot definitely establish the absence of any metformin hydrochloride extended release associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with metformin hydrochloride extended release, breastfeeding should be discontinued if the mother is treated with metformin hydrochloride extended release. Moreover, prolonged fasting is not recommended in pregnant woman * Women who practice any type of intermittent fasting program * Women who will not have anyone available to assist them in case of need

Inclusion Criteria: * Aged 18 - 75 years * Male or female * Participants who are otherwise healthy enough to participate, as determined by pre-study medical history * Participants who are able and willing to give written informed consent to participate in the study * Group A only: Patients requiring acute (\<5 days) high dose (minimum 30mg) oral prednisolone therapy for antiinflammatory purposes in either an inpatient or outpatient setting. * Group B only: Minimum of 1 month duration of high dose prednisolone (\>30mg) if in the chronic use group. * Group C only: Patients started on high dose methylprednisolone (\>3 day course) or prolonged courses of dexamethasone. Exclusion Criteria: * Participants with a diagnosis of Type 1 or Type 2 diabetes mellitus. * Unable to give informed consent. * Taking supplements or herbal medications that the participant is unwilling or unable to stop prior to and during the study period e.g. St John's Wort (may decrease prednisolone levels), Cat's claw, Echinacea (immunomodulatory properties). * Currently taking medications that alter CYP3A4 metabolism of glucocorticoids that the participant is unwilling or unable to stop prior to and during the study period e.g. phenytoin, phenobarbital, rifampicin, rifabutin, carbamazepine, primidone, aminogluethimide, itraconazole, ketoconazole, ciclosporin or ritonavir. * Pregnancy. Females of child-bearing age will be asked to provide a urine sample for a pregnancy test at each visit. * History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or compromise the safety of the participant.

Inclusion Criteria * Physical confirmed diagnosis of Multiple Sclerosis (MS) * Diagnosis of Major Depressive Disorder (MDD) - see below (MINI) * English as primary language * Eligible age (between 18 and 64 years old) * Relapse and steroid free in past 30 days * Internet and email access * Willingness to complete the testing and questionnaires, wear the accelerometer, undergo randomization, and engage in exercise testing Exclusion Criteria * Godin Leisure Time Exercise Questionnaire (GLTEQ): Exclude if health contribution score of 14 units or more. This assessment is administered to confirm insufficient baseline physical activity (i.e., not meeting current PA guidelines) * Patient Determined Disease Steps (PDDS): Exclude if score above '2' (i.e., greater than mild ambulatory disability). This assessment is administered as the proposed intervention focuses on walking as main modality for exercise training. The scale asks the participant to describe their walking situation on a scale of 0 to 8; where lower scores indicate better walking ability. * Beck Depression Inventory-Fast Screen (BDI-FS): Exclude if a score less than '4'. The scale measures depression and those with a score of '4' or below likely have very mild depression resulting in floor effects and/or spontaneous remission. * Physical Activity Readiness Questionnaire (PAR-Q): Exclude if more than one yes/affirmative response on this 7-item self-report assessment. This assessment is administered to exclude those individuals who are at a moderate to high risk for contraindications of injury or possible death when undertaking strenuous or maximal exercise. This is a 7-item self-report tool where more than one yes/affirmative response indicates that an individual is not recommended to engage in physical activity within the capacity of this study. Those scoring more than one yes/affirmative response will be further advised to seek medical guidance before becoming more physically active. * Telephone Interview for Cognitive Status (TICS-M): Exclude if scores less than 18. This assessment is administered to ensure that all participants can adequately follow directions. The application of the TICS-M is to ensure that participants do not have severe cognitive impairment that might preclude the ability to adhere to the conditions, understand intervention content, and interact with behavior coaches. * MINI International Neuropsychiatric Interview (version 7.0.2) based on the Diagnostic and Statistical Manual of Mental Disorders V (DSM-V): Include those who meet the criteria for MDD, but exclude for other severe mental illness (obsessive-compulsive disorder, schizophrenia, bipolar or other psychotic disorders) as indicated by the MINI; these persons would require more intensive mental health treatment.

Inclusion Criteria: The study population consists of children in the age group 1-5 years admitted to a pediatric ward, due to an acute episode with asthma-like symptoms. An acute asthma-like episode will be defined as annoying coughing, wheezing (wheezing or wheezing in connection with exhalation) and / or dyspnoea, which affects the child's well-being and requires hospitalization in a pediatric ward. Participation in the study requires that the child is in or has been in treatment with SABA, as monotherapy, or in combination with ICS, and possibly also in combination with LTRA in accordance with the Danish guidelines Exclusion Criteria: * The child is hospitalized with pneumonia * The child's daily intake of vitamin D supplementation is\> 400 IU / day (\~ 10 μg / day). * The child is given a combination of vitamin and dietary supplements containing vitamin D, thus the daily recommended dose is exceeded, as 2400 IU / day (\~ 60 μg / day) is accepted for children aged 1-4 years, as everyone here is recommended to take 400 IU / day (\~ 10 μg / day) by the Danish Health and Medicines Authority. * The baby has been exclusively breastfed for the past 6 months. * The child is malnourished * for children\> 2 years of age whose age-specific BMI is less than the 3rd percentile. * for children \<2 years, whose weight or height in relation to age is less than the 3rd percentile. * The child is a newly arrived refugee or immigrant from regions with a high risk of rickets. * The child has other chronic lung diseases. * The child is diagnosed with other conditions such as chronic lung disease, impaired renal function, neurological or psychiatric disorders, congenital or documented acquired QT prolongation, clinically relevant bradycardia, cardiac arrhythmia or severe heart failure and / or hepatic impairment. * The child is being treated with medication that alters calcium or vitamin D absorption / metabolism.

Inclusion Criteria: 1. Male or female, Age ≥18; 2. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1; 3. Histologically confirmed HER2 positive breast cancer, with HER2 positive defined by in situ hybridization (ISH), immunohistochemistry (IHC), or fluorescence in situ hybridization (FISH) methodology; 4. Documented isolated brain progression (defined as new or progressive brain metastases with stable or responding systemic disease) under pertuzumab and trastuzumab treatment (with or without taxane) for metastatic disease (There is no limit to the number and size of brain metastasis); 5. Complete local treatment of brain progression (Surgery and/or radiation therapy) should have been completed no more than 12 weeks before inclusion and there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator; 6. Able to undergo MRI scanning of the brain; 7. Normal renal function: creatinine \<1.5 x upper limit of normal (ULN); 8. Adequate liver function: total bilirubin ≤1.5 ULN (unless documented Gilbert's syndrome); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ULN (≤5 ULN in the presence of liver metastases); 9. Normal hematological function: Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L; platelets count ≥100 x 10⁹/L; and hemoglobin ≥9.0 g/dL; 10. Adequate cardiac functions, including: * 12 Lead electrocardiograms (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention * QT/Corrected QT interval (QTcF) ≤470 msec for woman and ≤450 msec for men (mean of replicate values, correction per institutional standard) on the ECG at the screening visit and a normal kalemia * Left ventricular ejection fraction (LVEF) ≥50% * No history of Torsades de Pointes or other symptomatic QTc abnormality 11. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 5.0 Grade 1 or to baseline (except alopecia or others toxicities not considered a safety risk for the patient at investigator's discretion); 12. Stable dose of steroids at the time of enrolment; 13. Women of childbearing potential must have a negative pregnancy test (blood or urine test) within 14 days prior to inclusion; 14. Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of trial participation and up to 7 months after completing treatment/therapy (association of trastuzumab, pertuzumab +/- tucatinib). Hormonal contraceptives such as birth control pills, patches, implants, or injections are not allowed in patients who are hormone receptor positive; 15. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent; 16. Patients affiliated to the social security system (or equivalent); 17. Patient must be willing and able to comply with the protocol for the duration of the trial including scheduled visits, treatment plan, laboratory tests, and examinations including follow-up. Exclusion Criteria: 1. Radiologic extra-cranial progression under pertuzumab and trastuzumab treatment, at the time of enrolment. The systemic disease must be stable or responding at the time of enrolment; 2. Proven leptomeningeal disease; 3. Any progressive brain lesion between the brain local treatment completion and the enrolment; 4. Poorly controlled seizures (more than 1/week); 5. Clinically significant cardiopulmonary disease; 6. Used of a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to first dose of study treatment. Use of sensitive CYP3A substrates should be avoided one week before enrollment and during study treatment 7. Previous treatment with a tyrosine kinase inhibitor; 8. Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease; 9. Positive for human immunodeficiency virus (HIV); 10. Known prior severe hypersensitivity to tucatinib or compounds chemically or/and biologically similar or any component in its formulation; 11. History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless the patient has been in remission and off all other cancer therapy for at least 3 years; 12. Pregnant women or women who are breast-feeding; 13. Inability to swallow tablets or significant gastrointestinal disease which would preclude the adequate oral absorption of medications; 14. Person deprived of their liberty or under protective custody or guardianship or unable to give informed consent; 15. Participation in another therapeutic trial within the 30 days prior to tucatinib treatment initiation.

Inclusion Criteria: 1. Ability to give written informed consent 2. Age \> 18 years at time of study entry. 3. Patient would be willing to undergo surgery is appropriate for surgery 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1). 5. Tumor size \> 1 cm to ≤ 3 cm assessed by ultrasound and clinically and radiographically node negative with no known metastatic disease. 6. HER2+ BC as defined by American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines.31 Patients may have ER+ or ER- negative disease, as defined by ASCO-CAP guidelines. 7. Left ventricular ejection fraction (LVEF) must be within institutional limits of normal as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan, documented within 4 weeks prior to first dose of study drug. 8. Adequate normal organ and marrow function as defined below: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (≥ 1500 per mm3) * Platelet count ≥ 100 x 109/L (≥100,000 per mm3) * Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). The maximum allowable bilirubin is ≤ 2.5 x ULN for patients with Gilbert's disease. * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN * Calculated glomerular filtration rate \>50 mL/min 9. Patients must either be of non-reproductive potential or willing to undergo appropriate contraception. Male subjects must agree not to donate sperm and female subjects must agree not to donate oocytes starting at screening and throughout the study period, and for at least 12 months after treatment discontinuation. 10. Patient with reproductive potential must have a negative pregnancy test ≤3 days prior to the first dose of zanidatamab. Exclusion Criteria An individual who meets any of the following criteria will be excluded from participation in this study: 1. Involvement in the planning and/or conduct of the study. 2. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen 3. Has received therapy for this current diagnosis of BC including investigational therapy, endocrine therapy, targeted therapy, or chemotherapy, surgery or radiation. 4. Mean QT interval corrected for heart rate (QTc) ≥ 470 ms. 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, active bleeding diatheses, , or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent. 6. Female patients who are pregnant, breast-feeding, or of reproductive potential who are not employing an effective method of birth control. 7. Patients with uncontrolled seizures. 8. Any major surgery for any reason, within 4 weeks of the enrollment. Portacath placement will be allowed. 9. Clinically significant cardiac disease such as ventricular arrhythmia requiring therapy, , myocardial infarction, unstable angina (within 6 months prior to first dose of study drug), any history of cardiac failure, and uncontrolled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications). 10. Known active Hepatitis B and/or Hepatitis C. Hepatitis testing is not required unless the patient has a history of Hepatitis B or C. 11. Known to be HIV positive. HIV testing is not required for those patients who are not known to be positive. 12. Total lifetime anthracycline load exceeding 360 mg/m2 doxorubicin or equivalent 13. Any condition that requires systemic treatment with either corticosteroids (\>10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤14 days prior to randomization. Note: Subjects who are currently or have previously been on any of the following steroid regimens are not excluded: 1. Adrenal replacement steroid (dose ≤10 mg daily of prednisone or equivalent) 2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption\\ 3. Short course (≤7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen) 14. History of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation 15. Known distant metastatic disease including (CNS) metastases, symptomatic CNS metastases, and leptomeningeal disease (LMD). 16. Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of subjects with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment) 17. Symptomatic pulmonary embolism ≤28 days 18. Administered a live vaccine ≤4 weeks prior to randomization. Patients can get COVID vaccine that are not alive before ot during the study period, with 48 hours between vaccine administration and investigation agent administration.

Inclusion Criteria: 1. Male or females 18-75 years old. 2. Subjects diagnosed with moderate-to-severe allergic asthma \[Global Initiative for Asthma \[GINA\]; GINA, 2021) at least 12 months prior to Visit 1. 3. Documented reversibility from historical data of at least 12% and 200 mL in FEV1 after the administration of 200 to 400 mcg albuterol/salbutamol (or other standard office practice) OR documented airway hyperresponsiveness (methacholine PC20 \< 8 mg/mL \[or PC20 \< 16 mg/mL on ICS\]) OR airflow variability in clinic FEV1 \>12% and 200 mL between visits outside of respiratory infections, documented in the past 24 months prior to Visit 1 if documented reversibility and airway hyperresponsiveness data are not available. 4. Subjects must have a pre-bronchodilator FEV1 value of ≥ 40% and ≤ 80% predicted within 2 months from randomization. 5. Subjects must have received a physician-prescribed asthma regimen with medium- or high-dose ICS plus LABA for at least 3 month prior to Visit 1 and the dose of ICS must be stable for at least 30 days prior to Visit 1 and throughout the screening period. 1. High-dose ICS is defined as total daily dose of \>500 mcg fluticasone propionate or equivalent 2. Medium-dose ICS is defined as a total daily dose of 250 to 500 mcg fluticasone propionate or equivalent. 3. Equivalence ICS doses will be based upon the GINA guidelines (GINA, 2021) 4. According to the medical history, subject have no more than a maximum of 2000 mcg/day equipotent ICS daily dosage of fluticasone propionate or equivalent in 3 months before visit 1. 6. Prior to screening, subjects must be on a stable dose of any of the following doses and formulations of ICS/LABA combination therapy for at least 1 month: 1. Fluticasone/salmeterol combination therapy * Advair® Diskus - dry powder inhaler (DPI): 250/50 μg BID or 500/50 μg BID, or * Advair® HFA - metered dose inhaler (MDI): 230/42 μg BID or 460/42 μg BID, or 2. Budesonide/formoterol combination therapy (Symbicort® -160/4.5 μg BID or 320/9 μg BID), or 3. Mometasone/formoterol combination therapy (Dulera® -200/10 μg BID or 400/10 μg BID). 4. Other equivalents medium to-high dose medication following the GINA guidelines (GINA, 2021) 7. Subjects must have a documented history of protocol-defined asthma exacerbation at least 1 or more times within the 12 months. 8. A total serum IgE ≥ 125 IU/mL during screening prior to randomization. 9. Subjects must have at least one positive in skin prick test or at least one environmental allergen-specific IgE greater than normal range. 10. Uncontrolled asthma demonstrated both during the screening period and at the time of randomization defined as ACQ-5 (5-item Asthma Control Questionnaire) ≥ 1.5 11. If recently treated for respiratory tract infection, the treatment must have been completed at least 4 weeks prior to screening. Subjects who have an upper respiratory tract infection during screening are allowed to be rescreened 4 weeks after resolution. 12. Female subjects of childbearing potential must use at least two forms of birth control. One must be barrier protection (i.e., condom or female condom) and the other is one of acceptable method of birth control (ie, diaphragm, intrauterine device, hormonal contraceptives, or abstinence) throughout the study. Subjects who are surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or postmenopausal (defined as amenorrhea for 12 consecutive months and documented serum follicle stimulating hormone level \>40 mU/mL) will be considered as no childbearing potential. All female subjects of child-bearing potential must have a negative serum pregnancy test at screening. Note: The subject must use the methods of contraception mentioned above during study period and at least 120 days after the last dosing of FB825. 13. The subject has a body weight ≥ 40 kg at screening. 14. The subject has a normal or non clinically significant abnormal, as determined by the investigator, 12-lead electrocardiogram (ECG). 15. The subject is able to provide written informed consent. 16. The subject agrees to comply with all protocol requirements. Exclusion Criteria: 1. Asthma exacerbation or any other reason requiring systemic steroids in the 30 days prior to randomization. Subjects are allowed to be rescreened 30 days after completion of treatment. 2. \>20% relative change in post-bronchodilator FEV1 between screening and randomization. 3. Female subjects who are pregnant or lactating. 4. A positive human immunodeficiency virus (HIV) test (e.g., HIV Ag/Ab combo test) at screening or subject taking antiretroviral medications, as determined by medical history. 5. Patients with positive HBeAg or HCV RNA results should be excluded as they are indications of active Hepatitis B virus and Hepatitis C virus replication. 6. Active lung diseases (e.g., bronchitis, chronic obstructive pulmonary disease) other than allergic asthma. 7. Use of any experimental drug within 30 days or 5 half-lives, whichever is longer, prior to or during the screening period. 8. Current or history of treatment with a monoclonal antibody, for example, IL-4, IL-5, IL-13 or IL-15 antibody treatment within 6 months prior to the screening. 9. Current or history of treatment with anti-IgE antibody treatment within 6 months or 5 half-lives, whichever is longer. 10. The subject has a history of alcohol or drug abuse that would impair or risk the patients' full participation in the study, in the opinion of the investigator. 11. The subject has any condition that, in the opinion of the investigator, would compromise the study or the well-being of the subject or prevent the subject from meeting or performing study requirements. 12. The subject has indication of severe liver disease, defined by serum levels of either alanine aminotransferase (ALT), aspartate transaminase (AST) above 3x upper limits of normal (ULN) or elevated total bilirubin \>2x ULN as determined at screening. 13. The subject has severe kidney disease, defined as estimated GFR \<30ml/min/1.73m2 or creatinine \> 3x ULN. 14. The subject has known or suspected history of immunosuppression or immunodeficiency. 15. Known history of active tuberculosis (TB) or evidence of tuberculosis infection as defined by a positive purified protein derivative (PPD) skin test and/or interferon-gamma release assay. The interferon-gamma release assay should be repeated in case of an indeterminate result. 16. The subject has history of malignancy within 5 years before the screening period. Patients with non-invasive carcinoma in-situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin may be eligible if they have undergone curative resection at least 12 months prior to screening. 17. Current smoker with \> 10 packs year prior to screening. A smoker is defined as a subject who has taken inhaled nicotine containing products (e.g. cigarette, cigar, pipe), including e-cigarettes prior to screening. 18. High risk of parasite infection • Risk factors for parasitic disease (living in an endemic area, travel within the last 6 months to regions where geohelminthic infections are endemic, and/or chronic immunosuppression). AND • Evidence of parasitic colonization or infection on stool evaluation for ova and parasites. Note: stool ova and parasite evaluation will only be conducted in patients with risk factors and an eosinophil count more than twice the upper limit of normal. 19. The subject has received live vaccine within 12 weeks or COVID-19 vaccination within 2 weeks prior to dosing or planned live attenuated vaccinations during the study. 20. The subject has a history of any clinically relevant arrhythmias as determined by the investigator. 21. The subject has a history of respiratory failure or near fatal asthma events which resulted in intensive care unit admission or intubation within five years before the screening period.

Inclusion Criteria: * 21-65 years old, Male/Female, East Asian population * 50 kg/m2≥BMI≥27.5kg/m2 * Type 2 diabetes duration ≥6 months * HbA1c≥7.0% * Currently receiving one or more oral/injectable hypoglycemic drugs (insulin /glucagon-like peptide-1 receptor agonist) * Recommendation for OAGB/RYGB evaluated by a multidisciplinary team Exclusion Criteria: * Underwent gastrointestinal surgery (gastric/duodenal surgery or bariatric surgery) * Fasting C-peptide level lower than 1/2 normal minimum * Active gastrointestinal ulcer is present * Helicobacter pylori infection is present * A history of serious cardiovascular and cerebrovascular diseases (myocardial infarction, stroke, etc.) * A history of cirrhosis (Child-Pugh≥A) * A history of chronic kidney disease (eGFR )\< 60 ml/min / 1.73 m2) * Inflammatory bowel disease is present (ulcerative colitis, Crohn's disease) * Chronic anemia is present, Hgb for male \<100g/L, for female \<90g/L * A desire to conception during the study period * Uncontrolled mental and psychological disorders are present * Expected survival\<5 years of end-stage disease or previous/current malignant tumor * Participated in clinical studies/trials that have the conflict of interest with the study * Unable to understand, refuse to participate and sign the informed consent * Gallstones require cholecystectomy * Reflux esophagitis above grade A

Inclusion Criteria: Screening Group: * Female sex of any ethnicity * Age 40 years or older * Scheduled for a routine screening mammography exam within 4 weeks. Diagnostic Group: * Female sex of any ethnicity * Age 30 years or older * Have an abnormality detected by Breast Self Exam (BSE), or Clinical Breast Exam (CBE), or have an abnormality detected by an imaging modality. * Will undergo diagnostic mammography, prior to breast biopsy (if needed). Exclusion Criteria: * Pregnancy * Lactation * Unknown pregnancy status AND * has refused pregnancy testing and * has refused to sign a pregnancy test waiver * Women who are unable or unwilling to understand or to provide informed consent * Women with physical limitations that may prohibit resting prone on the exam table, such as, but not limited to: frozen shoulder, recent heart surgery, pace maker. * Women who are unable to tolerate study constraints. * Women who have received radiation treatments to the thorax or breast area for malignant and nonmalignant conditions, such as (but not limited to): * Treatment for enlarged thymus gland as an infant * Irradiation for benign breast conditions, including breast inflammation after giving birth * Treatment for Hodgkin's disease * Women who have participated in a prior breast clinical trial that gave additional radiation dose, such as an additional mammogram. * Women who have received large numbers of diagnostic x-ray examinations for monitoring of disease such as (but not limited to): * Tuberculosis * Severe scoliosis Additional exclusion criteria due to machine limitations * Patient's body weight is over the limit of the scanner table (440 lbs. or 200kg)

Inclusion Criteria: * Age 50+ * English or Spanish proficiency * 24-item Hamilton Rating Scale for Depression score \> 15 * 12-item Fall Risk Questionnaire score \>4 Exclusion Criteria: * Recently (\< 4 weeks) initiated or modified antidepressant pharmacotherapy * High suicide risk * Probable dementia * Bipolar disorder * Substance use/misuse * Current participation in any psychotherapy or FP program * Bedbound status

Inclusion Criteria: * Male and female * BMI of 18.5-40 kg/m2 and weight stable over the previous 6 months. * Age, 18-64 years old. * Fasting glucose of 100-125 mg/dL or fasting HbA1c of 5.7-6.4%, or 2h OGTT blood glucose of 140-199mg/dL based on the American Diabetes Association criteria for pre-diabetes. Fasting glucose, HbA1c and OGTT results ordered by the participant's provider within 3-months of the screening visit will be accepted, provided they fall within the measurement of error range established by the institution's lab standards. Additionally, consistent use of Metformin (1 year) to prevent prediabetes from developing diabetes will be accepted. * Less than 150 minutes of moderate-to-vigorous physical activity (MVPA) per week and more than 6 hours of sitting time per day, as self-reported by the volunteers using the International Physical Activity Questionnaire (IPAQ). * Less than 6500 of steps per day as measured by a pedometer over 5 days (at least 1 weekend day). * Passing medical and physical screening, and analysis of blood and urine screening samples. * Low-moderate caffeine use (\<3 cups/day). * Agree to refrain from any other structured exercise than the physical activity prescribed in each arm of the study. * Agree to eat control diets for 3 days before and during the Clinical and Translational Research Center (CTRC) visits; * Agree to refrain from taking any over-the-counter (including nonsteroidal anti-inflammatory drugs) or prescribed medication (apart from oral contraceptives) for 3 days prior to the inpatient CTRC visits; * Agree to wear a Fitbit® activity monitor and upload data on the website on a daily basis for the whole duration of the study. * Agree to follow the physical activity interventions and to be randomly assigned to one of the two arms of the study. * Agree to complete all the study procedures. Exclusion Criteria: * Pregnancy, breast-feeding or post-menopause for women. * Being considered unsafe to participate as determined by the study physician. * Ever having a history of systemic, psychiatric, neurological disease, or drug and alcohol abuse. * History of cardiovascular disease, diabetes, uncontrolled hypertension, untreated thyroid, renal, hepatic diseases, dyslipidemia or any other medical condition affecting weight or lipid metabolism. * Being positive for human immunodeficiency virus or hepatitis B or C. * Taking medications affecting weight, triglycerides, energy intake/energy expenditure, or sleep in the last 3 months. * Having abnormal blood chemistry and/or hematology as deemed significant by the study physician. * Being a smoker or having been a smoker in the 3 months prior to their screening visit. * Having donated over 400 mL of blood within 3 months (90 days) of screening for the study; * Working night shifts within 1 month of and throughout the study. * Not completing the trial days of BREAK and ONE during the screening period to assess the willingness and ability of the participant to perform each of the interventions.

Inclusion Criteria: * Medication-free women with moderate to severe MD episode according to the Montgomery Asberg Depression Rating Scale (MADRS\>7), and peripartum onset, diagnosed before delivery or between the second week and month 6 postpartum * Between 18-45 years of age * Pregnancy to term * Uncomplicated delivery to a healthy newborn * Must be able to manage the technical aspects of the intervention. Exclusion Criteria: * tDCS contraindications * Previous experience with tDCS * Mental health disorder other than unipolar depression or anxiety * Suicidal ideation.

Aim 1 Inclusion Criteria: * Aged 18 or older * Head Start Staff member or caregiver of child currently enrolled in Head Start with asthma * Cognitive ability to provide consent * Willing to be audio recorded

Inclusion Criteria: * Have a diagnosis of ER+, HER2- locally advanced or metastatic breast cancer * Have disease that has demonstrated progression on or after an aromatase inhibitor alone or in combination with a cyclin-dependent kinase (CDK)4/6 inhibitor \-- Participants are expected to have received prior treatment with a CDK4/6 inhibitor, if this treatment is approved and can be reimbursed * Must be deemed appropriate for treatment with endocrine therapy * If female, have a postmenopausal status by natural or surgical means or by ovarian function suppression * Have RECIST evaluable disease (measurable disease and/or nonmeasurable bone-only disease) * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale (Oken et al. 1982) * Have adequate renal, hematologic, and hepatic organ function * Must be able to swallow capsules/tablets Exclusion Criteria: * Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, or any investigational-ER-directed therapy (including SERDs and non-SERDs), any PI3K-, mTOR- or AKT- inhibitor * Have visceral crisis, lymphangitic spread within the lung, or any evidence of leptomeningeal disease. * Have symptomatic or untreated brain metastasis. * Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study * Known allergic reaction against any of the components of the study treatment

Inclusion Criteria: * Diagnosis of major depressive disorder OR obsessive-compulsive disorder (DSM-V criteria) * Hamilton Depression Rating Scale score greater than or equal to 18 OR Yale-Brown Obsessive-Compulsive Scale score greater than or equal to 16 * Failed at least 1 prior trial of standard first-line treatment for depression or OCD per the modified Antidepressant Treatment History form and APA Practice Guidelines (e.g. serotonin reuptake inhibitor \[SRI\] or cognitive behavioral therapy with exposure and response prevention) OR had refused these treatments for individual reasons (e.g., cannot tolerate side effects, cannot tolerate exposure therapy, etc.). * Off antidepressants OR on a stable dose of antidepressants for greater than or equal to four weeks with plans to remain on this stable dose during the study Note: Medications that are known to increase cortical excitability (e.g., buprorion, maprotiline, tricyclic antidepressants, classical antipsychotics) or to have an inhibitory effect on brain excitability (e.g., anticonvulsants, benzodiazepines, and atypical antipsychotics), or any other medications with relative hazard for use in TMS will be allowed upon review of medications and/or motor threshold determination by TMS specialist. * Capacity to consent Exclusion Criteria: * Imminent risk of suicide (based on the CSSRS) * Presence of primary psychiatric diagnoses other than OCD, MDD and/or co-morbid GAD (ex. PTSD, MDD with psychotic features, primary psychotic illness, Bipolar I or II) * Evidence of cognitive impairment (MMSE score falling 1 SD below mean score for his/her age and education) * Evidence of psychotic symptoms on diagnostic interview (interfering with capacity to consent) * Have met criteria for any significant substance use disorder within the past 6 months * Recent onset (within 8 weeks of screening) of psychotherapy * Prior completion of this accelerated TMS treatment protocol during the current depressive episode * Participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening * Evidence or history of significant neurological disorder including moderate-severe head trauma, stroke, Parkinson's disease or other movement disorder (except benign essential tremor), epilepsy * History of seizures (except juvenile febrile seizures) or any condition/concurrent medication that could notably lower seizure threshold * Presence of foreign metal bodies/implanted intracranial devices (MRI contraindication) * Current pregnancy or planning to conceive during the study * Abnormal bloodwork for electrolytes, thyroid or liver function

Inclusion Criteria: * Adults with histologically-confirmed HER2 negative, unresectable locally advanced or metastatic breast cancer that is hormone receptor positive (HR+) at the time of the first breast cancer diagnosis * Participants with a documented radiologic unresectable or metastatic progression * Participants may have received anthracyclines and taxanes as (neo) adjuvant treatment and must have received one line of chemotherapy for Advanced breast cancer (ABC), but not more than one line. Participants must have a clinically or radiologically documented evidence of tumor progression on or after cyclin dependent kinase 4/6 (CDK 4/ 6) inhibitor combined with endocrine therapy. Previous treatments with PI3K inhibitors, mTOR inhibitors, AKT-inhibitors and poly ADP ribose polymerase (PARP)-inhibitors are allowed * Participants must have a tumor site easily accessible to biopsy (with exception of bone metastasis) * Participants must have at least one radiologically measurable lesion (different from the biopsy site) * Participants must have an ECOG PS equals to 0 or 1 * Participants must have a life expectancy of 12 weeks or more * Participants must have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1 * Female patients of reproductive/childbearing potential must have a negative pregnancy test at screening (serum test within 14 days or urine test within 72 hours of enrollment). A positive urine pregnancy test result must be confirmed by a serum test. Patients must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months after the last dose of study drug. The following contraception methods are considered highly effective: 1. Hormonal or nonhormonal intrauterine device (IUD) 2. Progestogen-only subdermal contraceptive implant 3. Bilateral tubal occlusion 4. Vasectomized partner 5. Complete sexual abstinence defined as refraining from heterosexual intercourse during and upon completion of the study and for at least 7 months for females after the last dose of study drug. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception. Penile/external condoms for male partners must be used in addition to the female patient's hormonal contraception for the duration treatment intervention and until 7 months following the last dose of trial intervention. Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration. * A male participant capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate each trial intervention. The length of time required to continue contraception after last dose for each trial intervention is 4 months. Avoid donating sperm. Note: Preservation of sperm should be considered prior to enrollment/randomization in this trial. Use a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential, PLUS partner use of an additional contraceptive method (see below), as a condom may break or leak: 1. Progestogen-only contraceptive implant 2. Hormonal or nonhormonal IUD 3. Bilateral tubal occlusion (includes tubal ligation) 4. Combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal, injectable) 5. Progestogen-only hormonal contraception (oral, injectable) 6. Progesterone-only hormonal contraception where inhibition of ovulation is not the primary mode of action 7. Cervical cap, diaphragm, or sponge with spermicide Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the trial interventions are more stringent than the requirements above, the local label requirements are to be followed. Note: If the participant is azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview), no contraception is required. Male participants must not freeze or donate sperm starting at screening and throughout the study period, and for at least 4 months after the final study drug administration * Participant must understand, sign, and date the written ICF prior to any protocol-specific procedures performed. Participant should be able and willing to comply with study visits and procedure as per protocol * Participant must be affiliated to a social security system or beneficiary of the same Exclusion Criteria: * Breast cancer amenable for resection or radiation therapy with curative intent * Any history of interstitial lung disease (ILD), actual ILD, or a suspicion of an ILD * Clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to: 1. Any underlying pulmonary disorder 2. Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement 3. OR prior pneumonectomy * The use of chronic systemic corticosteroids at a dose superior to 10 mg daily of prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study * Evidence of any leptomeningeal disease * Evidence of corneal disease * Any evidence of severe or uncontrolled systemic diseases including active bleeding diatheses, active infection, psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardize compliance with the protocol * Evidence of clinically active spinal cord compression or brain metastases defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms * Exposure to prior systemic anticancer therapy (including investigational agents) within 4 weeks or 5 half-lives (whichever is shorter) before enrollment. * Inadequate washout period prior to Cycle 1 Day 1, defined as: 1. Whole brain radiation therapy \<14 days or stereotactic brain radiation therapy \<7 days. 2. Immune checkpoint inhibitor therapy \<21 days 3. Hormonal therapy \<21 days 4. Major surgery (excluding placement of vascular access) \<28 days. 5. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation \<28 days or palliative radiation therapy \<14 days. 6. Chloroquine or hydroxychloroquine ≤ 14 days 7. Live virus vaccination \<28 days. * Prior treatment with an anti-HER3 antibody and/or ADC containing an exatecan derivative that is a topoisomerase I inhibitor * Participants with a grade equals or greater than 2 unresolved toxicities from previous anticancer therapy (other than alopecia) * A history of severe hypersensitivity reactions to either the drug substances or inactive ingredients of U3-1402, or to other monoclonal antibodies * Any evidence of primary malignancy other than locally advanced or metastatic lung cancer within three years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated * Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day : 1. Corrected QT interval higher than 470 ms for females and 450 ms for males according to Fridericia's formula (QTcF) and assessed based on triplicate ECGs, approximately 1 minute apa

Inclusion Criteria: 1. Age 18 or older and in good health 2. Each eye with one of the following qualifying diagnoses (diagnoses may differ between eyes): 1. High-risk ocular hypertension (OHT): IOP \> 21 mmHg without glaucomatous optic neuropathy (excavation, diffuse or focal thinning or notching of the neuroretinal rim, visible nerve fiber layer defects, or asymmetry of the vertical cup-to-disc ratio of \>0.2 between eyes) 2. Mild primary open-angle glaucoma: glaucomatous optic neuropathy, visual field mean deviation better than -6.0 dB with no points in the central 5° \<15 dB (see figure on next page) 3. Moderate primary open-angle glaucoma: glaucomatous optic neuropathy, visual field mean deviation equal to or worse than -6.0 dB but no worse than -12.0 dB and no central 5° points \<15 dB or mean deviation -12.0 dB or better with 1 central 5° points \<15 dB (see figure on next page). 3. Each eye with BCVA 20/200 (UK 6/60) or better Exclusion Criteria: 1. Use of topical IOP-lowering medications for more than 6 cumulative months at any time in the past 5 years (this is a modification implemented during active enrollment) 2. Any history of IOP-lowering laser (prophylactic iridotomy not included) or surgical procedure 3. Advanced POAG in either eye (worse than moderate POAG as defined above) 4. Glaucoma other than POAG (including pigmentary and pseudoexfoliation glaucoma) in either eye 5. Mean IOP \> 35 mmHg at either the screening or baseline visit in either eye 6. Narrow or closed angle (Shaffer Grade 0, 1, or 2) in either eye 7. Contraindications to SLT or any other study intervention 8. Any corneal pathology that would preclude accurate assessment of IOP by Goldmann tonometry in either eye 9. Any intraocular surgical procedure within the past 6 months in either eye 10. Inability to attend all scheduled study visits 11. Pregnant or planning to become pregnant in the next 4 years

Key Eligibility Criteria (additional criteria may apply) Part 1 Key Inclusion Criteria 1\. Pathologically confirmed solid tumors, e.g., Colorectal Cancer (CRC), Non-Small Cell Lung Cancer (NSCLC), or Pancreatic Cancer (PANC), that is metastatic, unresectable locally advanced, or in the Investigator's opinion the subject is high risk for incurable relapse within two years. Part 1: Key Exclusion Criteria 1. History of any of other malignancy in the past 5 years other than non-melanoma skin carcinoma, low grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the Cervix, or Stage I uterine cancer. 2. Prior allogeneic stem cell transplant. 3. Prior solid organ transplant. Part 2 : Key Inclusion Criteria 1. Pathologically confirmed solid tumors, e.g., Colorectal Cancer (CRC), Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer (PANC), Mesothelioma, or Ovarian Cancer (OVAC) that is metastatic, unresectable locally advanced, or in the Investigator's opinion the subject is high risk for incurable relapse within two years. 2. Participants are germline HLA-A\*02 heterozygous confirmed by HLA typing. 3. Primary tumor tissue showing LOH of HLA-A\*02 by NGS testing. 4. Eastern Cooperative Oncology Group (ECOG) 0 or 1 performance status. Part 2: Key Exclusion Criteria 1. History of any of other malignancy in the past 5 years other than non-melanoma skin carcinoma, low grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the Cervix, or Stage I uterine cancer. 2. Prior allogeneic stem cell transplant. 3. Prior solid organ transplant. 4. Participants who have received any cancer therapy on any investigational therapy for any indication, including but not limited to chemotherapy, small molecules, monoclonal antibodies, or radiotherapy (with bone marrow impact) within 2 weeks of planned apheresis or 3 half-lives, whichever is shorter. 5. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment necessitating specific treatment, or any major episode of infection requiring treatment with Intravenous (IV) antimicrobials (e.g., IV antibiotics) or hospitalization (relating to completion of antibiotic course). 6. Has known active central nervous system metastases. Subjects with previously treated brain metastases may participate upon medical monitor agreement. 7. In the Investigator's judgement, any other condition or reason the subject would not complete the required study visits and procedures, and follow up visits, or comply with the study requirements for participation.