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Inclusion Criteria: 1. Participant must be medically able to undergo the testing required in the schedule of events (SOE). 2. Participant's clinical diagnosis must be consistent with glaucoma characterized by the following features: Mean deviation (MD) of -3 to -20 dB on Humphrey Visual Field 24-2 testing and two visual field tests of adequate quality with a maximum VFI variability of ± 10% 3. Residual visual field preservation including best-corrected visual acuity (BCVA) better than 20/200 in either eye. 4. Participant's eye pressure must be clinically stable, with IOP \<21. 5. If a participant has two eyes meeting study criteria, the worse eye as determined by visual field index (VFI) or patient preference, will be deemed includable. If both eyes qualify and have the same VFI, a randomization procedure will assign one eye to the study. 6. Participant must understand and sign the informed consent. If the participant's vision is impaired to the point where he/she cannot read the informed consent document, the document will be read to the participant in its entirety. 7. Females of childbearing potential must agree to use an effective form of birth control. 8. Participant must be determined by the presurgical anesthesia or medical team to be fit for ophthalmic surgery for the NT-501 ECT implant insertion. Exclusion Criteria: 1. Participant is unable to comply with study procedures or followup visits. 2. Participant has other optic nerve or retinal degenerative disease causing vision loss, irrespective of whether it is currently treated or untreated. 3. Participant is likely to be offered glaucoma surgery in the study eye within 6 months of screening. 4. Participant has cataract-associated vision loss to less than 20/40. 5. Participant has a history of ocular herpes zoster. 6. Participant has a requirement of acyclovir and/or related products during study duration. To be eligible for this study, the participant must discontinue use of these products prior to enrollment and must not continue with the products until after they have completed the study. 7. Participant has evidence of corneal opacification or lack of optical clarity. 8. Participant has uveitis or other ocular inflammatory disease. 9. Participant is receiving systemic steroids or other immunosuppressive medications. 10. Participant has diabetic macular edema and/or diabetic retinopathy. 11. Participant has myopic degeneration. 12. Participant is currently participating in or has within the last 3 months participated in any other clinical trial of a drug by ocular (if in the study eye) or systemic administration. 13. Participant is pregnant or lactating. 14. Participant is on chemotherapy. 15. Participant has a history of malignancy other than basal cell carcinoma, unless it was treated successfully 2 years prior to inclusion in the trial. 16. Participant has, in the opinion of the investigator, any physical or mental condition that would increase the risk of participation in the study or may interfere with the study procedures, evaluations and outcome assessments. 17. Any intraocular surgery of the study eye within 12 weeks prior to the screening visit 18. History of use of drugs with known retinal toxicity, at retinotoxic doses. 19. Patient has a history of multiple sclerosis.

Inclusion Criteria: A. Prior to REGISTRATION 1\. Written informed consent prior to any study procedures (outcomes of standard-of-care procedures performed before signing of informed consent by the patient but within allowed screening period can be used for screening of patient). 2. Female. 3. ≥ 18 years of age. 4a. EITHER: (Post)menopausal status at the time of initiation of adjuvant study medication * patient underwent bilateral oophorectomy, or * age ≥ 60, or * age \< 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, or ovarian suppression) and/or FSH and estradiol in the postmenopausal range per local normal range. 4b. OR: Pre-/perimenopausal patients: * confirmed negative serum or urine pregnancy test (β-hCG) before starting study treatment, or * patient has had a hysterectomy. 5. Histologically confirmed diagnosis(by local laboratory ) of estrogen-receptor positive and/or progesterone-receptor positive (\>1% ) primary early breast cancer or local relapse. In case the receptor status from local pathology is unclear a central pathology review is obligatory. Results must be known prior to randomization. 6\. Patient has HER2-negative breast cancer defined as * a negative in-situ hybridization test or an IHC status of 0, 1+, or 2+, * if IHC is 2+, a negative in-situ hybridization (FISH, CISH, or SISH) test is required (based on the analyzed tissue sample at initial diagnosis by a local laboratory). 7\. Patients are eligible * with completed (i.e., 5 years according to SoC), planned or ongoing adjuvant endocrine therapy, without any signs of distant relapse or secondary malignancy AND * if primary diagnosis was 6 years or less before enrollment 8a. Intermediate to high clinical or genomic risk, defined as either one of the following criteria: * c or p or ypN 2-3 with/without (neo)adjuvant chemotherapy; * in patients with c/ypN0-1: * non-pCR in patients with G3 or c/ypN1 * high biological risk defined as G3 with Ki-67 ≥40% * or high genomic risk (RS\>25 (known or Oncotype Dx® in screening phase) or another test) * high CTS5 score or UICC stage IIb (clinical if neoadjuvant chemotherapy or pathological) OR, if patients do not fulfill above criteria: * patients ≤50 years old or pre-/perimenopausal and c or (y)pN1 disease (in particular if ET-non-response or no chemotherapy) * patients \>50 years old and postmenopausal and c or (y)pN1 with intermediate genomic risk (RS≥18) or non-low risk by another test ET non-response definition: Ki-67 post-treatment \> 10% (central or local pathology value) OR 8b. Patients after isolated locoregional relapse with high-risk patterns (e.g., rpT2-3 or rpN1-3 or G3 or Ki-67 pre-treatment ≥20%), once surgery with free margins was completed Note: Inclusion is only possible for the first locoregional relapse removed by surgery (free margins) OR 8c. Patients with any high clinical risk at Investigator´s assessment but not fulfilling above criteria: consultation with sponsor required B. Prior to RANDOMIZATION in the study 9. Completed primary therapy of breast cancer according to current guidelines, i.e., after (neo)adjuvant treatment, definite surgery and radiotherapy, if applicable. 10\. No clinical evidence of distant metastasis (confirmation recommended prior to randomization by either combination of or either one of the following examinations: CT thorax / abdomen, chest X-ray, liver ultrasound, bone scan, PET-CT). 11. Patient has available tumor tissue from primary diagnostic biopsy. 12. No contraindication for adjuvant ET. 13. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 14. Patient has adequate bone marrow and organ function as defined by the following laboratory values: * absolute neutrophil count ≥ 1.5 × 109/L, * platelets ≥ 100 × 109/L, * hemoglobin ≥ 8.0 g/dL, * total bilirubin ≤ 1.5 ULN, except for patients with Gilbert's Syndrome who may only be included if the total bilirubin is ≤ 2.0 × ULN or direct bilirubin within normal ranges, * aspartate transaminase (AST) ≤ 3 × ULN, * alanine transaminase (ALT) ≤ 3 × ULN, * serum creatinine ≤ 1.5 x ULN. 15. Ability to swallow abemaciclib tablets or to administer other study medication, respectively. 16\. Ability to communicate with the investigator and comply with study procedures. 17\. Willing to receive therapy by clinical site, as required by the protocol. Exclusion Criteria: Patients eligible for inclusion in this study must not meet any of the following criteria: 1. Patient with distant metastases of breast cancer beyond regional lymph nodes. 2. Previously received CDK 4/6 inhibitor. 3. Patient with a known hypersensitivity to any of the excipients of abemaciclib or standard-of-care endocrine therapy. 4. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects. 5. Patient has not recovered from clinical and laboratory acute toxicities related to prior anticancer therapies to NCI CTCAE version 5.0 Grade ≤ 1 (polyneuropathy ≤ 2 is allowed). 6. Patient has a concurrent malignancy or non-breast malignancy within 5 years prior to randomization. 7. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small-bowel resection). 8. Patient has any active systemic bacterial infection (requiring intravenous antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment. 9. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator´s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study, or compromise compliance with the protocol (e.g., interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea, etc.). 10. Patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. 11. Patient is currently receiving any of the following substances, which cannot be discontinued 7 days prior to day 1 of study treatment: o concomitant medications and herbal supplements, that are strong inducers or inhibitors of CYP3A4. 12. Participation in a prior investigational study within 30 days prior to enrollment. 13. Not able to understand and to comply with study instructions and requirements. 14. Pregnant or nursing (lactating) woman. 15. Woman of child-bearing potential defined as woman physiologically capable of becoming pregnant, unless she is using highly effective methods of contraception during the study treatment and for 21 days after stopping the treatment: 1. total abstinence (when this is in line with the preferred and usual lifestyle of the patient). 2. female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study treatment. 3. male partner sterilization (at least 6 months prior to study screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient. 4. placement of an intrauterine device (IUD). 5. use of condom + spermicide. 16. Use of oral (estrogen and progester

Inclusion Criteria: * Adults * Persons able to understand and object to the information provided. * Type 2 diabetic patient free of heart failure ≥stade B * Patient affiliated with a social security scheme. * Patient agreeing to sign the informed consent form Exclusion Criteria: * Patient with dementia * Patient with at least one of the criteria for heart failure ≥stade B

Inclusion Criteria: * Participants must meet the following criteria on screening examination to be eligible to participate in the study. Laboratory assessments for eligibility must be completed within 14 days prior to the date of registration. Diagnostic imaging, such as MRIs and CT scans, must be performed within 28 days of the planned treatment start. * Participants must have histologically or cytologically confirmed invasive breast cancer Stage I to III with primary tumor size at least 1.0 cm defined by physical exam or imaging (whichever is larger). In the case of a multifocal, multicentric, or bilateral disease, the largest lesion must be ≥ 1.0 cm and designated as the "index" lesion for tumor evaluations. Patients with inflammatory breast carcinoma are not eligible. * Participants must have documentation of estrogen receptor (ER) and progesterone receptor (PR) testing by IHC according to local institutional guidelines in a CLIA-approved setting. Central confirmation of ER/PR status is not required. All tumors must be HER2 negative. * Arms A and B: Target lesion must be ER and PR negative (\<10% staining) by local review. * Arm C: Target lesion must be ER and/or PR positive (\>10% staining) by local review. * Participants must have documented HER2-negative invasive tumor according to local institutional guidelines in a CLIA-approved setting. Central confirmation of HER2 status is not required. HER2 negative is defined as: * 0 or 1+ by IHC, OR * Lack of gene amplification with HER2/CEP17 ratio \< 2 by ISH, OR * Copy number \< 6 by ISH * Participants must have documented germline mutation in BRCA1, BRCA2 or PALB2 that is deleterious or suspected to be deleterious (known or predicted to be detrimental/lead to loss of function). Mutation must be identified through a CLIA-approved laboratory. Final determination of eligibility for any discordant results in pathogenicity will be made by the sponsor-investigator. A formal eligibility exception will not be required in these cases as long as approval by overall study PI is granted and documented. * Participants with multifocal, multicentric or bilateral disease are eligible if at least one lesion meets criteria for the study. In this circumstance, the investigator must determine which will represent the target lesion to be assessed for response. This should remain consistent throughout the study. The target lesion should be selected on the basis of its size (lesion with the longest diameter) and suitability for accurate repetitive measurements. * Participants with an eligible target lesion, and another small HER2+ tumor (for example, \< 6 mm), may be eligible for enrollment following discussion and agreement with the overall principal investigator. A formal eligibility exception will not be required in these cases as long as approval by the sponsor-investigator is granted and documented. * Female or male ≥ 18 years of age * Breast imaging should include imaging of the ipsilateral axilla. For subjects with a clinically positive axilla by physical examination or imaging, axillary tissue acquisition is not required. For patients with a clinically negative axilla by examination and imaging, tissue acquisition is not required. For equivocal imaging findings, tissue acquisition (a needle aspiration, core biopsy) is required. Sentinel Lymph Node (SLN) biopsy before neoadjuvant therapy is not allowed. * ECOG performance status of 0 or 1 * Adequate organ and bone marrow function as defined below: * Absolute neutrophil count (ANC) ≥ 1500/mm3 * Platelet count ≥ 100,000/mm3 * Hemoglobin ≥ 9 g/dl * Total serum bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), (≤2.0 in patients with documented Gilbert's Syndrome) * AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional ULN * Serum or plasma creatinine ≤ 1.5 × institutional ULN, OR calculated creatinine clearance \> 50 mL/min using the Cockcroft-Gault equation * International normalized ratio (INR) OR prothrombin time (PT) ≤1.5× ULN. Participants who are receiving anticoagulant therapy are eligible as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) must be ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * Premenopausal women must have a negative urine or serum pregnancy test within 7 days of treatment start. Women are considered non-childbearing (by other than medical reasons) if they: * are ≥45 years of age and without menses for \>1 year * have been amenorrhoeic for \<2 years without history of a hysterectomy and oophorectomy with a follicle stimulating hormone value in the postmenopausal range upon screening evaluation * are post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use an adequate barrier method throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient. * Male and female participants of childbearing potential must agree to adhere to adequate contraception as defined in the protocol for the duration of study participation and for 150 days after the last dose of study treatment. * Female participants must agree to not breastfeed during the study or for 150 days after the last dose of study treatment. * Participants must agree to not donate blood during the study or for 90 days after the last dose of study treatment. * Ability to understand and willingness to sign an informed consent document. * Ability to swallow and retain oral medication. * Patients undergoing breast conserving therapy (ie lumpectomy) should not have any contraindications to radiation therapy. * Participants must be willing to undergo the mandatory research biopsy at baseline and after 3 weeks on study treatment. Participants who undergo an attempted research biopsy procedure for the purpose of this protocol and in whom inadequate tissue is obtained are not required to undergo a repeat biopsy in order to continue on the protocol. Exclusion Criteria: * Stage IV breast cancer. * Concurrent therapy with any other investigational product * Prior treatment for the current breast cancer, including prior chemotherapy, immune therapy, hormonal therapy, radiation, or investigational therapy for this diagnosis. * Excisional biopsy of the primary tumor and/or excision of axillary lymph nodes, including SLNB, prior to study treatment. * Participants with a history of malignancy are ineligible except in the following circumstances: * Individuals with a history of invasive breast cancer are not eligible unless they have been disease-free for a minimum of three years. * Individuals with a malignancy history other than invasive breast cancer are eligible if they have no active malignancy and are deemed by the investigator to be at low risk for recurrence of that malignancy. * Individuals with the following cancer history are eligible: adequately treated nonmelanoma skin cancers, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma. * Other exceptions may exist following agreement with the sponsor-investigator * Patients with a diagnosis of immunodeficiency, or currently receiving systemic steroid therapy or any other form of immunosuppressive within 7 days prior to the first dose of study treatment. Use of local corticosteroid injecti

* INCLUSION CRITERIA: Patients: In order to be eligible for this study, MDD participants must meet all of the following criteria: 1. Aged 18 to 70 years old. 2. Female participants of childbearing potential must be using a medically acceptable means of contraception. 3. Participants must be in good general health as evidenced by medical history and physical examination. 4. Each participant must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document. 5. All participants must have undergone a screening assessment under protocol 01M0254, The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants . 6. Participants must fulfill DSM-5 criteria for major depression (MDD) without psychotic features, as based on clinical assessment and structured diagnostic interview (SCID-P). 7. Participants must have an initial score on the MADRS greater than or equal to 18 or HAM-D greater than or equal to 15 within one week of study entry. 8. Participants must be experiencing an MDE lasting at least four weeks. 9. Unmedicated participants in both Groups must be medication-free for at least two weeks (5 weeks for aripirazole, brexpiprazole, fluoxetine) prior to first screen visit. Medications will not be discontinued for the purpose of this study. 10. Participants must have their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists. 11. Participants must agree to adhere to the lifestyle considerations. Healthy Controls: In order to be eligible to participate in this study, control subjects must meet all of the following criteria: 1. Aged 18 to 70 years old. 2. Female participants of childbearing potential must be using a medically acceptable means of contraception. 3. Able to provide informed consent. 4. Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment. 5. Be enrolled in 01M0254, The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers or 17M0181, Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies . 6. Have their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists. 7. Agree to adhere to the lifestyle considerations. EXCLUSION CRITERIA: Participants with MDD who meet any of the following criteria will be excluded from participation in this study: 1. Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen). Any lab value that is two-times the upper limit or even lower values in the investigator s judgment. Creatinine level \>1.3 mg/dL. 2. Participants must be free of all prohibited medications or at least two weeks (5 weeks for aripiprazole, brexpiprazole, fluoxetine) prior to screen visit. These medications include antidepressants, anti-inflammatory drugs (except for study medication celecoxib), antipsychotics, anxiolytics, psychotropic drugs not otherwise specified (including herbal products), and sedatives/hypnotics. Medicated participants in Group B may continue their therapy. 3. Participants should not have taken Non-Steroidal Anti-Inflammatory Drug (NSAID)s for two weeks prior to the PET scan. Aspirin, corticosteroids (with the exception of topical steroids), or immunosuppressants (e.g. methotrexate) must not have been taken in the prior month. 4. Current psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-5. 5. Participants with a history of DSM-5 substance use disorder (except for caffeinei or nicotine dependence) within the preceding three months. In addition, participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use impairs function of daily lfe. 6. Participants who, in the investigator s judgment, pose a current serious suicidal or homicidal risk. 7. Participants who have a history of aggressive behavior towards others. 8. Participants who have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy). 9. Participants seeking treatment or a change in treatment and may be referred to the community or to another research study. 10. Are unable to travel to the NIH. 11. Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits. 12. Have an inability to lie flat and/or lie still on the camera bed for at least two hours, including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with the participant during the screening visit. 13. Are unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye. 14. Pregnancy. 15. HIV Infection. 16. Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the investigators. Healthy controls who meet any of the following criteria will be excluded from participation in this study: 1. Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen). 2. Participants must be free of all prohibited medications or at least two weeks (5 weeks for aripiprazole, brexpiprazole, fluoxetine) prior to screen visit. These medications include antidepressants, anti-inflammatory drugs (except for study medication celecoxib), antipsychotics, anxiolytics, psychotropic drugs not otherwise specified (including herbal products), and sedatives/hypnotics. 3. Participants should not have taken NSAIDs for two weeks prior to the PET scan. Aspirin, corticosteroids, or immunosuppressants (e.g. methotrexate) must not have been taken in the prior month. 4. Participants with a history of DSM-5 substance use disorder (except for caffeine or nicotine dependence) within the preceding three months. In addition, participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use impairs function of daily life. 5. Participants who have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy). 6. Are unable to travel to the NIH. 7. Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits. 8. Have an inability to lie flat and/or lie still on the camera bed for at least two hours, including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with the participant during the screening visit. 9. Are unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye. 10. Pregnancy. 11. HIV Infection. 12. Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the investigators. EXCLUSION O

Inclusion Criteria: * Meeting major depressive disorder diagnostic criteria using the structured clinical interviews for Diagnostic and Statistical Manual of Mental Disorders-5 and scoring more than 14 on the 17-item Hamilton rating scale for depression at two evaluations (one week apart) (Hamilton, 1967). * If on medication, patients' dosage must be stable for at least three months prior to entering the study, and they must be willing to maintain stable dosage for the duration of treatment * Age between 18 and 65 * Hebrew language fluency * Provision of written informed consent. Exclusion Criteria: * Current risk of suicide or self-harm * current substance abuse disorders * current or past schizophrenia or psychosis, bipolar disorder, or severe eating disorder requiring medical monitoring * history of organic mental disease * currently in psychotherapy

Inclusion Criteria: * Confirmation of HER2 positivity. All patients with HER2+ cancers will be allowed to enroll if they have leptomeningeal disease (LMD). Patients may be IHC 3+ and/or FISH-positive. IHC 2+ HER2 patients are eligible with reflex FISH-positive testing with the ratio ≥2.0. And/or patients with HER2 positive cells in the cerebral spinal fluid. * Participants may have concomitant brain metastases * Cerebrospinal fluid (CSF) sampling is required to document LMD if not documented by MRI. Participants are still eligible CSF is negative but LMD disease is documented on MRI * Life expectancy greater than 8 weeks * Consent to pretreatment tumor biopsy or retrieval of archival tissue * Normal renal (creatinine \<1.5 × upper limit of normal \[ULN\]), liver (bilirubin \< 1.5 × ULN, transaminases \<3.0 × ULN, except in known hepatic disease, wherein may be \<5 × ULN) and blood counts (white blood cells ≥2.5, neutrophils ≥1000, platelets ≥75,000, hemoglobin ≥8) * LVEF \>50% * KPS \>/= 60 * Patients with surgery within 14 days should have recovered from all effects of the surgery and be cleared by their surgeon * There is no limit on prior systemic or IT therapies * Must be willing to have an Ommaya reservoir placed and a candidate for an Ommaya reservoir placement * Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study. Contraception methods should start a minimum of 14 days before the first administration of study drug and continue for the duration of study treatment and for at least 7 months after the last dose of study treatment. * Ability to sign informed consent. * Patients may continue treatment with IV trastuzumab, pertuzumab, or other HER2-directed, hormonal, or chemotherapeutic agents if controlling systemic disease and leptomeningeal metastases that developed while on these therapies. In addition, at time of systemic progression, patients may start additional agents at the discretion of the treating physician according to criteria per protocol. Exclusion Criteria: * Current or prior participation in a study of an investigational agent or investigational device within 2 weeks of the first dose of study treatment * Cannot be on systemic agents (chemotherapy) that have Central Nervous System (CNS) penetration (temozolomide, carmustine, lomustine, etoposide, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan, and topotecan) unless they develop or have progressive or persistent leptomeningeal metastases while on these agent(s). See protocol for additional information regarding systemic therapies. * Major surgery or significant traumatic injury that has not been recovered from 14 days before the initiation of study drug * Symptomatic lung disease resulting in shortness of breath at rest * Women who are pregnant or breastfeeding * History of serious adverse event to any of the study drugs or study drug components * Whole Body Radiation Therapy (WBRT) is not allowed while patients receive IT trastuzumab/pertuzumab; however, focal stereotactic or palliative RT is allowed * Significant medical or psychiatric illness that would interfere with compliance and ability to tolerate treatment as outlined in the protocol

Inclusion Criteria: * HER2-positive T1 histologically confirmed invasive carcinoma of the breast. Patients must have node-negative (N0) or micrometastases (N1mi) breast cancer according to the AJCC 8th edition anatomic staging table. * If the patient has had a negative sentinel node biopsy, then no further axillary dissection is required, and the patient is determined to be node-negative. Axillary nodes with single cells or tumor clusters ≤ 0.2 mm by either H\&E or immunohistochemistry (IHC) will be considered node-negative. * Any axillary lymph node with tumor clusters between 0.02 and 0.2cm is considered a micrometastasis. Patients with a micrometastasis are eligible. An axillary dissection is not required to be performed in patients with a micrometastasis found by sentinel node evaluation. In cases where the specific pathologic size of lymph node involvement is subject to interpretation, the Sponsor-Investigator will make the final determination as to eligibility. The investigator must document approval in the patient medical record. * Patients who have one or more foci of T1aN0, ER+ (defined as \>10%), HER2-negative cancer in the ipsilateral breast, in addition to their primary HER2-positive tumor, are eligible. * For unifocal disease, all invasive disease must have been tested for ER and PR (for multifocal disease, see below). Either ER or PR must be positive, defined as ER ≥10% or PR ≥10%. ER- and PR-assays should be performed by immunohistochemical methods according to the local institution standard protocol. * HER2-positive by ASCO CAP 2018 guidelines. * Bilateral breast cancers that individually meet eligibility criteria are allowed. * Patients with multifocal or multicentric disease are eligible as long as each tumor individually meets eligibility criteria. * Patients with a history of ipsilateral DCIS are eligible as long as the patient has not received prior hormonal therapy. Patients with a history of contralateral DCIS are not eligible unless contralateral DCIS was diagnosed at least 15 years ago * ≤ 95 days between the date of protocol registration and the patient's most recent breast surgery for this breast cancer * Patients must have undergone definitive breast surgery for the current malignancy. All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy), with either a sentinel node biopsy or axillary dissection \-- All margins should be clear of invasive cancer or DCIS (i.e. no tumor on ink). The local pathologist must document negative margins of resection in the pathology report. If all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed. Likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed. Radiation therapy to the conserved breast is required. * Patients may have received up to 8 weeks of hormonal therapy as adjuvant treatment for this cancer. Patients should otherwise not have received prior hormonal therapy with the exception that hormonal therapy administered for less than 8-week duration at least 15 years ago is allowed. * Prior oophorectomy (including for cancer therapy) is allowed. * Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy. * Patients who have participated in a window study (treatment with an investigational agent prior to surgery for ≤2 weeks) are eligible. Patients must have discontinued the investigational agent at least 14 days before participation in this study. * Men and women with any menopausal status ≥18 years of age * ECOG Performance Status 0 or 1 * Participants must have normal organ and marrow function as defined below: * ANC ≥ 1000/mm3 * hemoglobin ≥8 g/dl * platelets ≥ 75,000/mm3 * AST and ALT both \<5x institutional ULN * Total bilirubin ≤ 1.5 mg/dL. For patients with Gilbert syndrome, the direct bilirubin should be \<institutional ULN * Serum creatinine ≤ 2.0 mg/dL OR calculated GFR ≥ 30mL/min * Left ventricular ejection fraction (LVEF) ≥ 50% * Post-menopausal patients must meet one of the following criteria: * Prior bilateral ovariectomy/oophorectomy * Age ≥ 60 years * Age \< 60 years with intact uterus and amenorrhoeic for ≥ 12 consecutive months prior to chemotherapy and/or endocrine therapy exposure (medication-induced amenorrhea is not acceptable to meet this criterion) * Age \< 60 years hysterectomized and FSH and plasma estradiol levels in the postmenopausal range according to local policies prior to chemotherapy and/or endocrine therapy exposure. * Willingness to discontinue contraceptive hormonal therapy, e.g. birth control pills, prior to registration and while on study * Premenopausal patients with intact uterus must have a negative serum or urine pregnancy test, including women who have had a tubal ligation and women less than 12 months from their last menstrual period. * Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of nonhormonal contraception or two effective forms of nonhormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment and for 7 months after the last dose of antibody treatment and 3 months after the last dose of hormonal treatment. * Patients must be willing and able to sign informed consent. * Patients must be willing to provide archival tissue for research purposes. * If patient is English-speaking, must be willing to fill out patient questionnaires. Exclusion Criteria: * Neoadjuvant or adjuvant chemotherapy for this breast cancer prior to enrollment is prohibited. * Any of the following due to teratogenic potential of the study drugs: * Pregnant women * Nursing women * Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragms, IUDS, surgical sterilization, abstinence, etc). Hormonal birth control methods are not permitted. * Men who are unwilling to employ adequate contraception (condoms, surgical sterilization, abstinence, etc). * Participants who are receiving any other investigational agents for treatment of breast cancer, unless specific approval is obtained from the Sponsor-Investigator. * Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge) * Patients with a history of previous invasive breast cancer. * Individuals with a history of a different malignancy are ineligible except for the following circumstances: * Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. * individuals with the following cancer are eligible regardless of when they were diagnosed and treated: cervical cancer in situ, and non-melanoma cancer of the skin. * Intercurrent illness including, but not limited to: ongoing or active, unresolved systemic infection, renal failure requiring dialysis, active cardiac disease, prior myocardial infarction (asymptomatic changes on EKG suggestive of old MI is not an exclusion), history of CHF, current use of any therapy specifically for CHF, uncontrolled hypertension, significant psychiatric illness, or other conditions that in the opinion of the investigator limit compliance with study requirements. Time and Motion Substudy Eligibility: * Participant must be enrolled at Dana-Farber Cancer Institute * Participant must not have discontinued pertuzumab following treatment cycle 1 * Participant must be able to tolerate subcutaneous administra

Inclusion Criteria: * Digestive or gynecological / breast cancer proven or suspected, requiring oncological treatment (chemotherapy or immunotherapy) * Major patient * Patients benefiting from a Social Security scheme or benefiting through the intermediary of a third party * Information note and collection of non-opposition after clear and fair information about the study Exclusion Criteria: * Linguistic or psychological refusal or inability to understand and / or sign the information and no-objection note * History of a cancer other than that allowing inclusion in the 5 years preceding inclusion

Inclusion Criteria: * Patients with a hypertension disorder in pregnancy and/or preeclampsia from the 20th amenorrhea week until the 26th ± 2 amenorrhea week. * Age between 18 and 40 years old. * Having given written consent. * Patients affiliated to a social security scheme. Exclusion Criteria: * Presence of pathologies interfering in a major way with vascular parameters: known multicomplicated diabetes treated before pregnancy, hypercholesterolemia known (or LDL\>130 mg/dl), multicomplicated connectivitis, proven cardiovascular disease (ischemic heart disease, stroke, arteriopathy of the lower limbs, heart failure), pre-existing known renal failure (serum creatinine \>125 µmol/L) and/or pre-existing proteinuria ≥ 300 mg/24h). * Cardiac arrhythmia. * Hepatitis C, HIV infection (assay performed within 6 months prior to diagnosis of pre-eclampsia). * Recent history of venous (pulmonary embolism, phlebitis) or arterial (myocardial infarction, unstable angina, stroke, transient ischemic attack), thrombotic event ≤ 3 months. * Patient already engaged in a therapeutic protocol. * Patients under legal protective measures. * Patients receiving State Medical Assistance.

Inclusion Criteria: * female; * ≥18 years; * surgery for breast cancer (unilateral and bilateral) including ALDN with \>6 lymph nodes removed; * can effectively communicate verbally in Danish; Exclusion Criteria: * surgery for breast cancer with SLNB or \< 6 nodes removed; * pre-existing lymphedema (primary or secondary); * previous treatment for breast cancer; * pace maker; * conditions known to cause swelling (pregnancy, congestive heart failure, chronic/acute renal disease, cor pulmonale, nephrotic syndrome, nephrosis, liver failure or cirrhosis, pulmonary edema, and thrombophlebitis or deep vein thrombosis in the arms).

Key Inclusion Criteria: * Participant has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory. One new or recent biopsy (collected at screening if feasible) or archival tumor block or slides (3 slides minimum from a surgical specimen, or 7 slides minimum from a core needle biopsy) must be provided. It is recommended to provide a tumor sample collected after the most recent progression or recurrence. * Chinese man or postmenopausal woman ≥ 18 years of age * Participant has identified PIK3CA mutation (as determined by a Novartis designated laboratory) * Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory. * Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH or SISH) test is required by local laboratory testing * Participant has either * Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation) OR * If no measurable disease is present, then at least one predominantly lytic bone lesion must be present (Participants with no measurable disease and only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation). * Participant has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer. * Participants may be: * relapsed with documented evidence of progression while on (neo) adjuvant endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease * relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression while on or after only one line of endocrine therapy for metastatic disease * newly diagnosed advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy * Patient has ECOG performance status 0 or 1. * Patient has adequate bone marrow function. Key Exclusion Criteria * Participant with symptomatic visceral disease or any disease burden that makes the Participant ineligible for endocrine therapy per the investigator's best judgment. * Participant has received prior treatment with chemotherapy (except for (neo)adjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor. * Participant has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant. * Participant has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to randomization, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or from whom ≥ 25% of the bone marrow was irradiated. * Participant has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer. * Participant with an established diagnosis at screening of diabetes mellitus type I or not controlled type II * Participant has currently documented pneumonitis/interstitial lung disease * History of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis * Participant with unresolved osteonecrosis of the jaw * Participant has a history of severe cutaneous reactions like Stevens- Johnson-Syndrome (SJS), Erythema Multiforme (EM), or Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Other protocol-defined inclusion/exclusion criteria may apply.

Inclusion Criteria * Part 1: Breast Cancer (BC) * Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) BC * Part 1A/Part 1D/Part1E also include: Refractory HR-positive/HER2-positive BC * Part 1: Tumors other than BC (Part 1A/Part 1D/Part 1E): NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests * Part 1F: prostate cancer * Part 2A, 2B, 2C and 2E: * HR-positive/HER2-negative BC * Patients who are either postmenopausal women or pre/peri-menopausal (Part 2C only) * Part 1D: metastatic castration resistant prostate cancer * Lesion: * Part 1: evaluable lesion (including skin or bone lesion only) * Part 2A, 2B, 2C and 2E: measurable lesion per RECIST v1.1 * Part 2D: Participants with evaluable disease as per PCWG3; participants with bone metastases only are allowed. Participants with biochemical recurrence only are excluded. * Prior systemic Treatment * Part 1: HR-positive/HER2-negative BC * At least 1 line of SOC, including CD4/6 inhibitor therapy for advanced or metastatic disease, or if CDK4/6 inhibitors are not considered appropriate in the opinion of the investigator * At least 1 line of anti-endocrine in countries without CDK4/6 inhibitor approval or reimbursement, for advanced or metastatic disease * HR-positive/HER2-positive BC (Parts 1A/1D/1E): at least 1 prior treatment of approved HER2 targeting therapy * Tumors other than BC (Parts 1A/1D/1E/1F): tumor that is resistant to at least 2 lines of SOC for advanced or recurrent disease or for which no standard therapy is available * Part 2A and 2E: participants must have received at least 1 line of standard of care (including prior CDK4/6i) for advanced/metastatic disease; Prior chemo is allowed; Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed * Part 2B: participants who have not received any prior systemic anti-cancer therapies for advanced/metastatic BC * Part 2C: * Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre or perimenopausal, or * Progressed while on or within 1 month after the endo the prior aromatase inhibitor therapy for advanced/metastatic BC if postmenopausal or prior endocrine treatment for advanced/metastatic BC if pre or perimenopausal * One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy * Part 2D: * Received prior abiraterone; enzalutamide and CDK4i naive * 0-1 line of chemotherapy is allowed General Inclusion Criteria * All participants must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 * Adequate renal, liver, and bone marrow function Exclusion Criteria: * Part 1D: participants who have had a gastrectomy or have dietary or other restrictions that preclude a 10 hour overnight fast or consumption of the high fat, high calorie meal * Part 2B: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor with disease recurrence while on or within 12 months of completing treatment. Prior treatment with any CDK4/6 inhibitor * Part 2C: prior treatment with any CDK inhibitor, fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway * Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases carcinomatous meningitis, or leptomeningeal disease * Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ * Major surgery or radiation within 4 weeks prior to study intervention * Last anti-cancer treatment within 2 weeks prior to study intervention * Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry * Pregnant or breastfeeding female participant * Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or GI disease

Inclusion Criteria: * Histologically-confirmed, primary, invasive breast cancer diagnosed within 5 years of entry into the companion DTC screening protocol UPCC 28115 * Qualifying risk status, at diagnosis utilizing receptor testing by ASCO/CAP guidelines, meting at least one of the following: (i) Lymph node involvement a. Pathologically-confirmed positive axillary lymph nodes, regardless of receptors, or (b) Evidence of lymph node involvement by preoperative imaging AND fibrosis and/or treatment effect in lymph nodes after neoadjuvant therapy, regardless of receptor status (ii) Primary tumor that is ER/PR/Her2 negative: estrogen receptor (ER) \< 10%, progesterone receptor (PR) \< 10% and negative for Her2-overexpression by ASCO-CAP guidelines, regardless of lymph nodes status (iii) Primary tumor that is ER+/Her2 negative/Lymph node negative with Breast Cancer Recurrence Score of \>/= 25 per the Genomic Health Oncotype DX breast cancer test and/or high risk MammaPrint (iv) Evidence of residual disease in the breast on pathologic assessment after neoadjuvant chemotherapy * Patients must have completed all primary therapy (definitive surgery, (neo)adjuvant chemotherapy adjuvant radiation and/or Her2-directed therapy) for the index malignancy at least 4 weeks prior to study entry. Prior treatment-related toxicity must be resolved or improving to Grade 1 with the exception of alopecia, Grade 2 endocrine disorders (e.g. adrenal insufficiency or thyroid disorders from prior immunotherapy) controlled on stable replacement therapy for \> 1 year, and up to Grade 3 peripheral neuropathy, prior to study enrollment. Concurrent receipt of adjuvant endocrine and bone modifying agents is allowed per standard of care guidelines. Tamoxifen is not allowed due to drug-drug interactions with HCQ. * Bone marrow aspirate obtained via research trial UPCC 28115 after completion of therapy (except endocrine therapy) demonstrates detectable DTCs (via IHC) * No evidence of recurrent local or distant breast cancer by physical examination, blood tests (CBC, LFTs, Alk Phos), or imaging. Assessment for overt metastatic disease by radiologic testing per institutional guidelines (CT Chest, Abdomen and Pelvis, bone scan, MRI and/or PET/CT) will only be done in patients with DTCs detected on bone marrow aspirate who are being screened for this trial. * Age \>/= 18 years * ECOG performance status =/\< 2 * Ability to swallow oral medications * No contraindications to the study medications or uncontrolled medical illness. * Adequate bone marrow function as shown by: ANC \>/= 1.5 x 10\^9/L, Platelets \>/= 100 x 10\^9/L, Hb \>9 g/dL * Adequate liver function as shown by: Serum bilirubin \</= 1.5 x ULN, ALT and AST \</= 3.0 x ULN, and INR \</=1.5 * Adequate renal function: serum creatinine \</= 1.5 x ULN * Adequate muscle function: creatinine phosphokinase (CPK) \</= 2.5 x ULN * Anticoagulation is allowed if target INR =/\< 1.5 on a stable dose of warfarin or on a stable dose of anticoagulant for \>2 weeks at time of randomization * Ability to provide informed consent Exclusion Criteria * Concurrent enrollment on another investigational therapy * Patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to randomization (or treatment assignment), or is currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study. * Prior treatment with abemaciclib is not allowed. (Patients may have received prior CDK4/6 inhibitor therapy with an agent other than abemaciclib. Patients must have discontinued CDK4/6 inhibitor at least 6 months prior to screening.) * Known hypersensitivity to hydroxychloroquine or any of its derivatives * Prior hydroxychloroquine exposure for a duration of \> 1 month since the completion of the patient's primary therapy (definitive surgery, (neo)adjuvant chemotherapy, adjuvant radiation, and/or Her2-directed therapy) for the index malignancy. * Patients with hormone-receptor positive breast cancer may not be receiving tamoxifen due to drug-drug interactions with hydroxychloroquine * Patients who have initiated bone modifying agents within 3 months prior to the start of study treatment * Patients who have had major surgery within 14 days prior to randomization (or treatment assignment) * Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study * Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. * Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of Abema

Inclusion Criteria: * Single agent and combination dose exploration study：Patient is an adult male/female 18\~70 years old; the phase II study：Patient is an adult male/female ≥ 18 years old; * Single agent dose escalation study ：Patients with a histologically or cytologically confirmed diagnosis of a solid tumor for which Standard treatment failure or no further effective standard treatment is available. Combination dose exploration study：Patients with locally advanced or metastatic breast cancer with hormone receptor positive (HR+) and her2-negative (HER2-) were not eligible for surgical resection or radiotherapy for the purpose of cure, and had no clinical indications for chemotherapy, and received endocrine therapy ≤1 line. The phase II study: Locally advanced or metastatic breast cancer diagnosed histologically or cytologically not suitable for surgery or radical radiotherapy; HR+ and HER2- ; have locally advanced disease not amenable to curative treatment by surgery or metastatic disease; progress after previous endocrine therapy; at least 1 chemotherapy regimen in the previous adjuvant or metastasis contains paclitaxel; there should be at least 2 prior chemotherapy regimens; * At least one measurable lesion (based on RECIST v1.1); * Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; * Have recovered from the acute effects of therapy (until the toxicity resolves to either baseline or Grade 1) except for residual alopecia; * Adequate organ and marrow function; * The life expectancy of the patient was determined by the investigator to be ≥12 weeks; * Fertile male or female patients must agree to use an effective contraceptive method during the study period and for three months after the last study medication; * Patient has signed informed consent before any trial related activities. Exclusion Criteria: * Single agent and combination dose exploration study：Patients with known uncontrolled or symptomatic CNS metastases; The phase II study：Have central nervous system (CNS) metastasis, or Have visceral crisis, or Inflammatory breast cancer. * Have received an autologous or allogeneic stem-cell transplant. * Patient has impairment of gastrointestinal (GI) function or GI disease. * Single agent and combination dose exploration study：Any other malignancy was diagnosed within 3 years prior to enrollment, except for basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the cervix, which is adequately treated and the disease is stable. The phase II study：Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years. * Subject has impaired cardiac function or heart disease of clinical significance. * Cerebrovascular accidents within 6 months before enrollment, including a history of transient ischemic attack or stroke. * Major surgery or surgical treatment due to any cause occurred within 4 weeks prior to enrollment. * Presence of any serious and/or uncontrolled disease in the opinion of the investigator that may interfere with the study assessment. * Uncontrollable pleural effusion, peritoneal effusion, pericardial effusion in the 4 weeks before the first administration (except for a small amount of effusion detected by imaging examination). * A prior history of definite neurological or psychiatric disorders, including epilepsy or dementia. * Chronic active HBV, HCV or HIV diseases. * Patient who received any CDK4/6 inhibitor or patients who plan surgery, or the investigator determines that surgery or radical radiation therapy is required. * Participation in a prior treatment of chemotherapy, radiotherapy, endocrinotherapy, targeted therapy, immunotherapy and any investigational study within 14 days prior to enrollment. * Bone marrow suppression therapy, such as GCS-F, EPO, or blood transfusion, was administered within 14 days prior to enrollment. * Patient with a known hypersensitivity to any of the excipients in this study. * Pregnant or breastfeeding. * The researchers considered that there were some cases that were not suitable for inclusion.

Inclusion Criteria: * adult patients * Cirrhosis * intubation and mechanical ventilation Exclusion Criteria: * pregnancy * oliguric patients * impossibility to measure intravesical pressure

Inclusion Criteria: * Female participants, with at least 18 years old on the day of signing the free and informed consent; * Invasive breast carcinoma stage III (RH positive) or IIB/III (RH negative), according to TNM 8th edition; Histologically confirmed diagnosis of invasive breast carcinoma (with any histology), HER-2 negative; * The participant (or legally acceptable representative, if applicable) provides written informed consent for the study; * The participant must agree to use a contraceptive as detailed in Appendix B of this protocol during the treatment period and for at least 120 days after the last dose of the study treatment; * Have a functional capacity according to the Eastern Cooperative Oncology Group (ECOG) from 0 to 2. The evaluation of the ECOG must be carried out within 7 days before the inclusion date. * Have adequate organic function. The samples must be collected within 60 days before the start of the study treatment; * Have adequate cardiac function as assessed by echocardiogram or MUGA performed up to 60 days before the start of treatment under study. Exclusion Criteria: \- Individuals who do not meet the inclusion criteria above-mentioned.

Inclusion Criteria: * Patients scheduled to undergo mitral valve surgery by cardiopulmonary bypass with estimated mean pulmonary artery pressure =\>55 estimated by using preoperative Doppler echocardiography Exclusion Criteria: Patients were excluded if they had surgery without CPB, preoperative hemodynamic instability (defined as acute requirement for vasoactive support or mechanical device),Patients with severe LV dysfunction (LV ejection fraction of less than 30% congenital heart disease, a contraindication to transesophageal echocardiography (TEE), emergency surgery or re-do surgeries severe renal or hepatic disease , coagulopathy, and thromboembolic disease treated with anticoagulants

Inclusion Criteria: 1. Subject must have a disease of interest. Specifically, subject must have one of: 1. head and neck squamous cell carcinoma (HNSCC) 2. non-small-cell lung cancer (NSCLC) 3. small cell lung cancer (SCLC) 4. urothelial carcinoma (UCC) 5. gastric or gastroesophageal junction adenocarcinoma 6. cervical cancer 7. esophageal squamous cell carcinoma (ESCC) 8. triple-negative breast cancer (TNBC) 9. hepatocellular carcinoma (HCC) 10. renal cell carcinoma (RCC) 11. colorectal cancer (CRC) 2. Subject must have received, or be scheduled to receive, at least one dose of anti-PD-1/PD-L1 immunotherapy for treatment of their cancer. 3. Subject must have had, or will have, a tumor biopsy prior to treatment with anti-PD-1/PD-L1 immunotherapy. 4. Subject must have undergone, or will undergo, medical imaging (e.g. CT or MRI) of the tumor prior to treatment with anti-PD-1/PD-L1 immunotherapy. 5. Willing to provide electronic informed consent per IRB-approved protocol. 6. Able to speak, read, and comprehend English fluently. 7. Subject is 18 years of age or older. 8. Subjects must have sufficient tissue available to fulfill the specimen requirements of the study. Exclusion Criteria: 1. Inability or unwillingness to provide informed consent. 2. Subject who does/did not have one of the cancers listed above (other histologies). 3. Subject has already participated in this trial.

Inclusion Criteria: Men and post-menopausal women: * Having a body mass index (BMI= 25-40 kg/m2) * Aged between 45 and 74 years * Having confirmed menopausal status (FSH ≥ 30 U/l) * Non-smoker * Sedentary (less than 2 hours of structured physical exercise (ex: sports club) per week) * Low alcohol consumption: less than 2 alcoholic drinks/day Exclusion Criteria: * Plasma LDL cholesterol \> 3.5 mmol/L (i.e. \> 75th percentile in a Canadian population). * Elevated risk of cardiovascular disease (≥ 20% of calculated Framingham Risk Score) who would require immediate medical intervention by lipid-lowering agents. * Prior history of cardiovascular events (like stroke, transient ischemic attack, myocardial infarction, angina, heart failure…) * Systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg * Type 1 or 2 diabetes or fasting glucose \> 7.0 mmol/L * Prior history of cancer within the last 3 years * Thyroid disease - untreated or unstable * Anemia - Hb \< 120 g/L * Renal dysfunction or plasma creatinine \> 100 µmol/L * Hepatic dysfunction - AST/ALT \> 3 times normal limit * Blood coagulation problems (i.e. bleeding predisposition) * Autoimmune and chronic inflammatory disease (i.e. celiac, inflammatory bowel, Graves, multiple sclerosis, psoriasis, rheumatoid arthritis, and lupus).Known history of difficulties accessing a vein * Claustrophobia * Sleep apnea * Seizures * Concomitant medications: Hormone replacement therapy (except thyroid hormone at a stable dose), systemic corticosteroids, anti-psychotic medications and psycho-active medication, anticoagulant or anti-aggregates treatment (Aspirin, NSAIDs, warfarin, coumadin..), adrenergic agonist, anti-hypertensive drugs, weight-loss medication, lipid lowering medication * Known substance abuse * Already taking more than 250 mg of omega-3 supplements (EPA/DHA) per day * Allergy to seafood or fish * Allergy to Xylocaine * Unable to eat the components of the high fat meal (croissant, cheese, bacon, brownies) * None compliance to the study requirements (i.e. not being fasting) or cancellation of the same scheduled testing visit more than once. * Lack of time to participate in the full length of the study (33 weeks) * Have exceeded the annual total allowed radiation dose (like X-ray scans and/or tomography in the previous year or in the year to come) according to the physician's judgement. * All other medical or psychological conditions deemed inappropriate according to the physician