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Inclusion Criteria: * Males or females aged ≥ 18 to ≤ 75 years at the time of signing the ICF; * Histologically and/or cytologically confirmed HR+/HER2- breast cancer based on pathology reports on recent biopsy specimens or other pathological samples; * Patients who had failed at least one line of systemic chemotherapy in unresectable locally advanced, recurrent, or metastatic stage; * Patients with at least one measurable lesion per RECIST 1.1 criteria; those with only skin or bone lesions cannot be included; * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; * Expected survival ≥ 12 weeks; * Adequate organ and bone marrow function; * Patients who are eligible for a chemotherapy regimen in the control group; * Female patients of childbearing potential and male patients with partners of childbearing potential who use effective medical contraception from the time of signing the informed consent form until 6 months after the last dose; * Patients who voluntarily participate in the study and sign the ICF, and able to comply with the visit and related procedures stipulated in the plan. Exclusion Criteria: * Patients with a history of central nervous system (CNS) metastases or current CNS metastases； * Patients with other malignancies (except cured basal or squamous cell skin cancer or carcinoma in situ of the cervix) within 3 years prior to the first dose; * Patients with any cardio cerebral Vascular disease or cardio cerebral vascular risk factors may affect investigational treatment; * Uncontrollable systemic diseases assessed by the investigator; * History of (noninfectious) interstitial lung disease (ILD)/noninfectious neumonitis requiring steroid therapy and current ILD/noninfectious pneumonitis, or ILD/noninfectious pneumonitis at screening that cannot be excluded by imaging; * Clinically serious lung injuries caused by lung diseases; * Patients with active chronic Inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess or acute gastrointestinal bleeding; * Toxicities from prior anti-tumor therapy not recovering to ≤ Grade 1; * Active hepatitis B or hepatitis C; * Human immunodeficiency virus (HIV) antibody test positive or a history of acquired immunodeficiency syndrome (AIDS), known active syphilis infection; * Known allergy or hypersensitivity to SKB264, or the excipients of SKB264; * Prior TROP2 targeted therapy, prior topoisomerase I inhibitor therapy, including antibody-drugconjugate(ADC) therapy; * Patients who received major surgeries 4 weeks prior to the first dose of study treatment or planned to receive major surgeries during the study ; * Patients with concomitant infections requiring systemic antibiotic therapy within 2 week prior to the first dose of study treatment; * Patients who have received live vaccines within 30 days prior to the first dose, or are scheduled to receive live vaccines during the study; * Pregnant or lactating women.

Inclusion Criteria: 1. Men and women of age: 40.0 - 70.0 years 2. BMI: 18.0 - 25.0 kg/m2 (lean subjects) and BMI 30.0 - 38.0 kg/m2 (Ob-IS and Ob-IR) 3. Fasting insulin \< 9.0 mU/l (lean and Ob-IS subjects) and fasting insulin \> 9.0 mU/l (Ob-IR) 4. Fasting glucose \< 6.1 mmol/l 5. Body temperature \< 37.5°C 6. First-degree relative with known T2D in Ob-IR 7. Weight stable ± 5 kg \< 3 months before screening 8. Fluent in Swedish and can follow given instructions 9. Consent given to participate Exclusion Criteria: 10. First-degree relative with known T2D in lean or Ob-IS subjects 11. Alcohol intake \> 10 units/week or known high alcohol intake \< 10 years back in time 12. Daily use of cigarettes or daily frequent use of smokeless tobacco not enabling the participant to suspend nicotine during a visit at the research center without getting abstinent 13. Regular physical activity corresponding to Saltin-Gimby level 4 14. Special diet eg Atkins or 5:2 for weight reduction. Vegetarian food accepted if duration \> 1 year 15. Impaired fasting glucose (IFG) (venous fasting plasma glucose 6.1-6.9 mmol/l) 16. Type 2 diabetes according to ADA criteria 17. Ongoing or previous ischemic heart disease, eg angina pectoris, unstable angina or previous myocardial infarction treated with platelet inhibitors or non vitamin-K oral anticoagulants 18. Heart failure (NYHA II-IV) or cardiac arrhytmia that needs medical treatment 19. Previous cerebral infarction or transitory ischemic episodes (TIA) treated with platelet inhibitors or other anticoagulants 20. Peripheral arterial insufficiency eg claudication 21. Hypertension \>170/105 mmHg at screening or more than one class of drugs for treatment of known hypertension 22. Lipid disorder defined as fasting serum triglycerides \> 5.0 mmol/l or serum cholesterol \> 7.5 mmol/l 23. Hematologic diseases such as anemia not being substituted (Hb \< 130 g/l in males and Hv \< 120 g/l in females) or disease causing bleeding disorder 24. Renal failure defined as absolute estimated glomerular filtration rate (eGFRcreatinine) \< 60 ml/min/1.73 m2 25. Hypothyroidism defined as TSH \> 4.0 mIE/l and symptoms 26. Liver disease e.g. hepatitis B, cirrhosis or conditions where AST or ALT are \> 2 times UNL 27. Systemic inflammatory disease e.g. rheumatoid arthritis, ulcerative cholitis or Chrons disease. Celiac disease, dyspepsia or IBS are excepted 28. Chronic bronchitis or chronic obstructive pulmonary with disease symptoms 29. Previous pancreatitis or other disease in pancreas that needs treatment 30. Migraine elicited by stress 31. Spinal insufficiency causing inconvenience lying in supine position during the study day 32. Drug addiction interfering with the study procedures 33. Psychiatric insufficiency interfering with the study procedures 34. Medication with potential to affect adipose tissue metabolism that can not be stopped 10 days before the study days 35. Treatment with beta-blockers 36. Less than three months from previous use of antibiotics 37. Cancer disease \< 5 years since diagnosis 38. Physical examination or laboratory results indicating that participation in the study is inappropriate 39. Pregnancy or intention to be pregnant during the study 40. Shift work \> 1 time per week that might interfere with the circadian rhytm 41. Other reasons that causes the PI to believe that participation is inappropriate

Inclusion Criteria: * Mild traumatic brain injury (mTBI) defined in accord with the World Health Organization criteria in the last 12 months * age 18-65 at the time of the mTBI * high burden of post-concussive symptoms defined as a score \>=20 on the Rivermead Post-Concussion Symptoms Questionnaire Exclusion Criteria: * objective neurologic deficits * ongoing or prolonged (\>3 months) post-concussive symptoms from a prior mTBI within 2 years of the index injury * history of transcranial magnetic stimulation (TMS) therapy * contraindications for TMS or magnetic resonance imaging (MRI) (e.g., metallic implant other than dental, pacemaker) * severe mental, physical, or medical problems that would impede participation or pose a risk for the planned intervention (e.g., liver, kidney, or heart disease, uncontrolled diabetes or hypertension, malignancy, psychosis, previous seizure, pregnancy) * active alcohol or illicit drug abuse * inability to speak and read English

Inclusion Criteria: * must be diagnosed with type 2 diabetes * must be from rural Kentucky * must be living in rural Kentucky for at least 1 year Exclusion Criteria: * potential participants without consent

Inclusion Criteria: * women aged 18 years and older who identify as Chinese, Korean, or Japanese; * have had a breast cancer diagnosis in the past; * can read and write English, Mandarin (simplified or traditional), Korean, or Japanese; * have access to the internet through computers or mobile devices (mobile phones and tablets); * have experienced cancer pain during the past week (at least 1 on a scale from 0 to 5 \[no symptom=0, mild symptom that does not bother=1, somewhat bothering symptom=2, moderate symptom=3, severe symptom=4, and worst possible symptom=5\]); * have experienced depressive symptoms during the past two weeks (1 to 10 on the Patient Health Questionnaire) which is equivalent to the cut-point of minimal to moderate depression. Exclusion Criteria: * less than 18 years old because their cancer experience would be different from that of adults. * Those who are in treatment or not in treatment, but who were diagnosed with breast cancer within the past five years, will be excluded. * Those who participated in the PI's pilot studies will be excluded. * The participants of R33 phase will exclude those in active depression treatment regardless of their level of depression. * Those without Internet access will be excluded, but those with Internet access through community/group computers will be included.

Inclusion Criteria: * Eligible for inclusion will be patients diagnosed with CRSwNP according to the European Position Paper on Rhinosinusitis and Nasal Polyps that fulfill the criteria for initiating treatment with biologics as standard of care \[49\], suffering or not from comorbid severe asthma (CRSwNP + AS, CRSwNP - AS, respectively) who will consent to participate in the study. The study will not influence prescribing of mepolizumab to patients. Eligible to treatment women in childbearing potential will be informed before consent that they must take care of contraception and potential pregnancy during therapy as there is not enough data regarding the use of mepolizumab during pregnancy. All patients with severe asthma will be qualified for treatment with mepolizumab in accordance with GINA guidelines. Exclusion Criteria: * Patients less than 18 years of age, subjects suffering from COPD, known or suspected immunodeficiency or autoimmune disease, chronic interstitial lung diseases, cystic fibrosis, individuals exposed to systemic corticosteroid/immunosuppressive treatments, biologics for asthma care or antibiotics within the previous 3 months before mepolizumab administration, active smokers and obese individuals will be excluded from this study. Pregnant women will not be included into the study because of the potential changes that their microbiome and other host parameters could undergo during pregnancy. The control group will comprise healthy volunteers who will be free from CRS, asthma, and atopy.

Inclusion Criteria: * Pathologically confirmed HER2 positive advanced breast cancer * Age\>18 years. * Brain metastases confirmed by enhanced brain MRI. Metastases number less than 15. * KPS≥70 or KPS ≥60 with neurologic symptoms caused by BM * Life expectancy of more than 6 months * Prior therapy of oral dexamethasone not exceeding 16mg/d * Time interval from prior therapy was more than 2 weeks, and evaluation of adverse events is no more than grade 1. * Screening laboratory values must meet the following criteria( and should be obtained within 28 days prior to registration): 1. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets≥ 90 x 109/L, Hemoglobin ≥ 90 g/L 2. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 x ULN without liver metastasis,≤ 5 x ULN with liver metastases 3. Serum BUN and creatinine ≤ 1.5 x Upper Limit of Normal (ULN) 4. LVEF ≥ 50% 5. QTcF \< 480 ms 6. INR≤1.5×ULN，APTT≤1.5×ULN * Signed the informed consent form prior to patient entry Exclusion Criteria: * Leptomeningeal or hemorrhagic metastases * Uncontrolled epilepsy * Severe or uncontrolled disease: severe cardiovascular disease, end-stage renal disease, severe hepatic disease, history of immunodeficiency, including HIV positive, active HBV/HCV or other acquired congenital immunodeficiency disease, or organ transplantation history, active infection, etc. * History of allergy to treatment regimens * Pregnancy or lactation period， women of child-bearing age who are unwilling to accept contraceptive measures. * Inability to complete enhanced MRI * Not suitable for inclusion for specific reasons judged by sponsor

Inclusion Criteria: * Age over 18 * Patient is scheduled for gender mastectomy surgery (including nipple sparing mastectomy and mastectomy with free nipple graft) or NSM with breast implant or autologous reconstruction * Patient is capable and willing to provide informed consent Exclusion Criteria: * Patient has a nerve condition that does not allow for assessment of sensation * Any subject who at the discretion of the Investigator is not suitable for inclusion in the study or is unlikely to comply with follow-up schedule * Currently prescribed medication known to impact nerve regeneration or to cause peripheral neuropathy * Bilateral reconstruction with non-uniform treatment (i.e. 1 reconstructed breast is non-neurotized, 1 reconstructed breast is neurotized)

Inclusion Criteria: 1. adults (18-65 years old) 2. able to provide consent 3. are able to read and understand English 4. PHQ-9 score between 10-20, indicating moderate but not severe depressive symptom severity (27) 5. Must have filled out the waiver for the community-based yoga studio prior to enrolling in the study. Exclusion Criteria: 1. have had a bone fracture or joint surgery in the past 6 months 2. not able to walk freely or without difficulty 3. have severe heart failure or lung disease 4. participants endorse an item on the revised Physical Activity Readiness Questionnaire (PAR-Q+) and do not have approval from their treating physician (we will check in with treating physician in the event that participants endorse any item on the PAR-Q+) 5. participants must have a physician responsible for their medical care 6. are pregnant or planning to become pregnant 7. no more than 6 yoga classes in the past 6 months 8. have active suicidal thinking (i.e., PHQ-9 item 9 ≥1 and a positive response to C-SSRS screener items 3, 4, 5, or 6) 9. report manic symptoms (Altman Self-Rating Mania Scale score ≥ 6 (28)) 10. are on medications that make dehydration more likely (e.g., lithium, antipsychotics, insulin-dependent) 11. active eating disorders or substance use disorders within the past 12 months 12. antidepressant or psychiatric medications that are initiated less than 8 weeks or a dose change less than 4 weeks prior to screening visit 13. psychotherapy that has been initiated within the past 3 months 14. willingness to keep psychiatric medications and psychotherapy stable throughout the course of the study 15. psychiatric hospitalization within the past year 16. diagnosed with any neurological disorders that would impact participation or make participation unsafe 17. are currently in any active ketamine, ECT, or TMS 18. are unable to follow the study procedures (e.g., not able to travel to the heated or non-heated yoga studios)

Inclusion Criteria (diabetic group): * Diabetes mellitus type I or II, minimal duration of the disease 3 years, minimal duration of specific treatment (drugs, insulin) 2 years Exclusion Criteria (diabetic group): * Diabetes mellitus type II being treated with a diet only * Severe acute decompensation of diabetes (uncontrolled diabetes) necessitating hospitalization * Concomitant treatment with more than one prokinetic agent * Active treatment with opioids or a history of treatment with opioids within 12 months before enrolment * Previous esophageal or major gastric surgery (e.g. esophageal myotomy, esophagectomy, antireflux surgery, Billroth I or II gastric resection, gastric pull-through, pyloromyotomy, pyloroplasty, gastric electrical stimulation) * Organic pyloric (or intestinal) obstruction (fibrotic stricture, etc.) * Severe coagulopathy * Esophageal or gastric varices and /or portal gastropathy * Advanced liver cirrhosis * Pregnancy or puerperium * Malignant or pre-malignant gastric diseases (dysplasia, gastric cancer, GIST): patients with a history of such disease after its cure are eligible for enrolment * The presence of a rumination syndrome or eating disorders (anorexia nervosa, bulimia). In case of doubts, a psychiatric examination will be performed. * Systemic connective tissue disorder * Inability to obtain informed consent * Any other condition, which in the opinion of the investigator would interfere with study requirements

Inclusion Criteria: 1. Major Depression Disorder (MDD) or Bipolar Disorder (I /II) diagnosed by Structured Clinical Interview for DSM-V (SCID I/DSM-V) 2. Age 18 - 65 years. 3. 24-item Hamilton Depression Rating Scale (HDRS) score of at least 21 on the first 17 items and/or Montgomery-Asburg Depression Rating Scale (MADRS) score of at least 21. 4. World Health Organization Disability Assessment Scale 2.0(WHODAS2.0) score of 19 or more 5. A recurrent (equal or \>4 episodes) or chronic (episode duration equal or higher \>2 years) course AND a minimum of 5 years since the onset of the first depressive episode. Major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior) over lifetime history as determined by an investigator 6. As determined by the study psychiatrist/investigator, has treatment resistant depression defined as failure to respond to: 6.1. Adequate trials (equal or \>6 weeks at an adequate dose) of primary antidepressants from at least 3 different classes AND; 6.2. adequate trials (equal\>4 weeks at an adequate dose) of augmentation/combination of a primary antidepressant using at least 2 different augmenting/combination agents (lithium, T3, stimulants,neuroleptics, anticonvulsants, buspirone, or a second primary antidepressant) AND; 6.3 An adequate trial of ECT (\>6 bilateral treatments), or inability to tolerate an adequate ECT trial, AND; 6.4 An adequate trial of individual psychotherapy (\>20 sessions with an experienced psychotherapist). 7. Able to comply with the operational and administrative requirements of participation in the study. 8. Able to give written informed consent 9. Major Depressive Disorder (MDD) or Bipolar Disorder (I/II) is the primary psychiatric diagnosis in the medical opinion of an investigator. 10. On a stable psychiatric medication regimen beginning at least 6 weeks prior to enrollment and continuing through the first 6 months of the study, as determined by the investigator. Psychiatric medication changes can be made during the entirety of the subject's study participation but would be limited to the clinical judgment of the PI/study psychiatrist. 11. At enrollment, provides the following information from at least two (2) verifiable contacts who reside within a 10-mile radius of the patient: name, relationship to patient, address (email mail); and telephone (mobile, home, work as applicable). 12. Agrees to allow medical records requests and communications of any type to any and all health care providers who have seen the patient within five years of screening or enrollment. 13. For the duration of study participation, agrees to be followed by a licensed psychiatrist and/or other licensed mental health practitioner on a regularly scheduled basis. 14. FOR AGES 18-21: An average of at least 3 in the following subdomains on the Psychological Maturity Scale (PMS): questions 1-6, "Ego Resilience"; questions 7-13, "Self-Awareness"; questions 14-17, "Autonomy"; questions 18-21, Flexibility". 15. FOR AGES 18-21: Residing with a caretaker or having oversight of a caretaker. Exclusion Criteria 1. Patients with any lifetime history of psychosis or psychotic disorder, according to DSM-V diagnostic criteria, or in the medical opinion of the PI/study psychiatrist. 2. Any finding on the preoperative magnetic resonance imaging (MRI) scan that, in the opinion of the principal investigator and after consultation with the neuroradiologist, is, or might be, considered clinically significant such that participation in the study: (a) seems likely to increase the medical risk to the subject sufficient to outweigh the potential benefit to study participation; (b) seems likely to jeopardize the subject's ability to complete the study or fulfill all study requirements per protocol; or (c) may impact he integrity of the data or the validity of the results. 3. Any previous surgery to destroy the treatment target (superolateral MFB) rendering it either unilaterally or bilaterally damaged such that it cannot be effectively stimulated, as visualized by pre-operative MRI scans, in the medical opinion of the PI 4. Any surgical contraindications to undergoing DBS, including labeled contraindications for DBS and/orinability to undergo presurgical MRI (cardiac pacemaker, implantable defibrillator or other implantablestimulator, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy, inability to undergo an awake operation, significant cardiac or other medical risk factors for surgery. DBS contraindications include patients who are unable to properly operate the neurostimulator, and patientswho will be exposed to MRI or diathermy. MRI and diathermy (e.g., shortwave diathermy, microwave diathermy or therapeutic ultrasound diathermy) are contraindicated because the energy can be transferred through the implanted System (or any of the separate implanted components), which can cause tissue damage and can result in severe injury or death. Diathermy can damage parts of the neurostimulation system. 5. Refusal of an adequate trial of ECT in the medical opinion of the study psychiatrist or PI following consultation with a study psychiatrist. 6. History of stimulation intolerance in any area of the body. 7. Within six (6) months of the enrollment date, has been diagnosed with, or has met the diagnostic criteria for, a substance abuse disorder (SUD) according to DSM-V criteria. 8. Women of childbearing potential who, at enrollment or during the study: (a)have a positive urine pregnancy test; (b) are heterosexually active without the usage of a medically acceptable, highly effect contraceptive method\* (≤1% pregnancy rate); or (c) are planning to become pregnant during the 60-month course of this study, as determined by the PI. \*Examples include tubal ligation, vasectomized partner, IUD or IUS (intrauterine device or system), and long-acting reversible contraceptives (LARC). 9. Active suicidal ideation with intent, suicide attempt within the last six months, more than three suicide attempts within the last two years, or serious suicide risk as determined by the study psychiatrists. 10. Participation in another drug, device, or biologics trial within the preceding 30 days 11. Presence of a condition requiring routine MRIs. 12. Presence of a condition requiring diathermy. 13. Subject is on anticoagulant medication. 14. Prior to enrollment or during the course of the study and in the opinion of the PI, has a history of an medical, psychiatric, physical or non-physical disease, disorder, condition, injury, or disability; or has a non-medical reason (e.g., financial, logistical, personal, other) that: (a) may pose a significant risk to the patient; (b) may increase the possibility that the subject is unlikely to successfully complete all of the requirements of the study according to the study protocol; or (c) may adversely impact the integrity of the data or the validity of the study results. 15. Subjects without a fixed home address or stable living situation, in the opinion of the Principal Investigator. 16. Subjects involved in activities involving significant radiation exposure in the past year. 17. Receiving TMS after DBS implantation 18. Any mania or manic episodes within 5 years of enrollment according to DSM-V diagnostic criteria, or in the medical opinion of the PI/study psychiatrist

Inclusion Criteria: * diagnosis of open-angle glaucoma or ocular hypertension * qualifying IOP in the study eye Exclusion Criteria: * unmedicated (washed out) IOP of \>36 mmHg in the study eye * hypersensitivity to travoprost or any other components of the travoprost intraocular implant * vertical cup/disc ratio \> 0.8 in the study eye * best spectacle corrected visual acuity of worse than 20/80 in either eye * any ocular disease or condition that, in the opinion of the investigator, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study

Inclusion Criteria: 1. Chinese aged 12-20 years old. 2. Written informed consent of participation into the study is given by the participant and his/her parent or guardian (for those aged under 18). 3. Being able to comply with the study protocol. 4. Having a DSM-5 diagnosis of depressive disorders. 5. Having a score of ≥ 40 on Children's Depression Rating Scale (CDRS-R). 6. Having a score of ≤ 41 on Horne-Östberg Morning-Eveningness Questionnaire (MEQ; classified as evening chronotype). 7. Having a sleep onset time of 11:15pm or later for 12 year olds, 11:30pm or later for 13-14 year olds, and 12:00pm or later for 15-20 years at least 3 nights per week in the past 3 months. Exclusion Criteria: 1. A current diagnosis of substance abuse or dependence; a current or past history of manic or hypomanic episode, schizophrenia spectrum disorders, neurodevelopmental disorders, organic mental disorders, or intellectual disabilities. 2. Initiation of and change of medication that may interfere with circadian rhythm within past 3 months (e.g., lithium, exogenous melatonin, melatonergic antidepressants). 3. In the opinion of the research clinician, having a clinically significant suicidality (presence of suicidal ideation with a plan or an attempt). 4. Having been enrolled in any other clinical trial investigational products within one month at the entry of the study. 5. Initiation of or change in antidepressant medication within past 3 months. 6. Having been or is currently receiving any structured psychotherapy. 7. With hearing or speech deficit. 8. Night shift worker. 9. Trans-meridian flight in the past 1 month and during intervention. 10. Presence of an eye disease (e.g., retinal blindness, severe cataract, glaucoma).

Inclusion Criteria: Must have an identifiable chronic condition. Exclusion Criteria: Healthy Population

Inclusion Criteria: * age between 15 and 30 years * subjects meeting CAARMS criteria for stage Ia or Ib mental states at risk (for stage Ia, mild or nonspecific symptoms of psychosis or severe mood disorder, and mild functional impairment; for stage Ib, moderate symptoms below intervention threshold and moderate functional impairment) * subjects meeting any DSM-5 criteria associated with a first onset of psychotic symptoms (first episode psychosis) * subjects satisfying DSM-5 criteria for depressive disorder * subjects meeting DSM-5 criteria for autism spectrum disorder * healthy control subjects recruited from the general population Exclusion Criteria: * suicidal risk * severe or non-stabilized somatic and neurological disorders * epilepsy * head trauma * IQ below 70 * for healthy control subjects, a family history of psychosis is an exclusion criterion * bipolar disorder * obsessive-compulsive disorder * substance use disorder, except for cannabis, tolerated up to 5 joints/day.

Inclusion Criteria: The following inclusion criteria will be applied: 1. Patients male or female aged at least 70 years old at the time of informed consent. 2. Histologically or cytologically confirmed diagnosis of HR-positive (defined as estrogen-receptor ≥ 1%), HER2-negative breast cancer according to analysis of the most recent tumor specimen by local laboratory. 3. Advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative treatment. 4. No prior systemic treatment for advanced disease (recurrence during neo-/adjuvant endocrine therapy is allowed). A prior period of treatment with aromatase inhibitors or fulvestrant for up to 28 days from the CDK 4/6-inhibitor initiation is allowed. 5. Adjuvant treatment with CDK 4/6-inhibitors is allowed provided a disease-free interval from treatment end \>12 months. 6. Either measurable disease or non-measurable bone only disease, but evaluable according to RECIST criteria 1.1. 7. Written informed consent prior to any study-specific procedures. 8. Adequate organ function as defined in the summary of product characteristics (SmPC) for the CDK 4/6-inhibitors that is planned to be used. 9. Able to swallow capsules. 10. Able to understand and consent in English language or in native language for each participating country. Exclusion Criteria: Eligible patients will be excluded if they have one of the following criteria: 1. Patients considered from treating physician as non-suitable for treatment with CDK 4/6-inhibitors. 2. Contraindications according to SmPC for the CDK 4/6-inhibitors that is planned to be used. 3. Presence of visceral crisis, lymphangitis carcinomatosis, or leptomeningeal carcinomatosis. 4. History of any other cancer (except of non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years. 5. Participating in other interventional trial.

Inclusion Criteria: 1. Female patients ≥ 18 years and ≤ 75 years old; 2. Primary invasive breast cancer confirmed by histology; 3. HER2 positive breast cancer (IHC 3+, or IHC 2+ and FISH positive); lymph node positive, except for T0; lymph node negative and tumor \>1cm, or tumor \> 0.5 cm and ≤ 1cm, and accompanied by any of the following high-risk factors: pathological grade 3, ER/PR negative, or \< 35 years old; 4. Having received mastectomy or breast conserving surgery, and received sentinel lymph node biopsy or axillary lymph node dissection, and within 90 days from the breast surgery; 5. With known ER/PR status of breast cancer; 6. ECOG score 0-1; 7. The patient's major organ functions meet all of the following requirements for blood tests: 1. Neutrophil count (ANC) ≥ 1,500/mm3 (1.5×109/L); 2. Platelet count (PLT) ≥ 75,000/mm3 (75×109/L); 3. Hemoglobin (Hb) ≥ 8 g/dL (80 g/L); 4. Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 60 mL/min; 5. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); 6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 2.5 times the upper limit of normal (ULN), patients with liver metastases should be ≤ 5×ULN. 9\. The participant voluntarily joins the study, signs the informed consent form, has good compliance, and cooperates with follow-ups. Exclusion criteria: 1. Breast cancer recurs before enrollment, or local recurrence/ metastasis confirmed by radiology; 2. The subject has participated in other clinical trials within 4 weeks or 5 half-lives (whichever is longer) before enrollment; 3. The patient has previously received treatment including tyrosine kinase inhibitors targeting HER2 (e.g., lapatinib, neratinib, and pyrotinib); 4. The patient has been diagnosed with other malignancies within 5 years of enrollment, except for cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin which has been cured; 5. The patient is receiving anti-tumor therapies from other clinical trials; 6. Inability to swallow, chronic diarrhea, or intestinal obstruction, with multiple factors affecting drug administration and absorption; 7. The patient has undergone major surgical procedures unrelated to breast cancer within 4 weeks of enrollment, or has not fully recovered from such surgical procedures; 8. With known allergies to any components of the agents to be administered in this study; history of acquired or congenital immunodeficiency diseases, including HIV; history of HCV, active hepatitis B, or history of organ transplantation; 9. Pregnant and lactating patients, patients of fertility unwilling to take effective contraceptive measures throughout the trial; 10. With any heart disease including: (1) arrhythmia requiring medication or clinical attention; (2) myocardial infarction; (3) heart failure; (4) any other heart diseases that are considered unsuitable to the trial; 11. With any comorbidities that are considered to potentially endanger the patient's safety or interfere with the study, including but not restricted to resistant hypertension, severe diabetes, active infection, etc.; 12. With a history of neurological or mental disorders, including but not restricted to epilepsy or dementia; 13. The patient is using CYP3A4 inhibitors or inducers, or any other drugs that potentially prolong the QT interval; 14. Any other circumstances in which the researcher believes that the patient is not suitable to participate in this study.

Inclusion Criteria: * Female sex * Age between 50 and 67 (both included) years. * Invited for the regular breast cancer mammography screening program * Signed an informed consent Exclusion Criteria: * Personal history of breast cancer * Known high risk of breast cancer * Ethnic origin, for which the risk model has not been validated.

Inclusion Criteria: 1. Male or Female, between the ages of 18 and 80 at the time of screening. 2. Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information. 3. Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5). 4. MADRS score of ≥20 at screening (Visit 1). 5. TMS naive for one of the following areas: DLPCF or DMPFC 6. The dose of the primary antidepressant medication (if applicable) must be stable for 6 weeks prior to baseline, and participant must agree to continue at this dose throughout the study period. 7. In good general health, as evidenced by medical history. 8. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation. 9. Agreement to adhere to Lifestyle Considerations throughout study duration. Lifestyle Considerations: * Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 10). * Abstain from caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) for 3 hours before the start of each dosing session until after the final TMS session. * Abstain from alcohol for 24 hours before the start of each dosing session until after collection of the final MRI. * Participants who use tobacco products will be instructed that use of cigarettes will not be allowed during the study. Exclusion Criteria: 1. Pregnancy 2. History of or current psychotic disorder or bipolar disorder 3. Severe borderline personality disorder. 4. Diagnosis of Intellectual Disability or Autism Spectrum Disorder 5. Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder 6. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal 7. Urine screening test positive for illicit substances 8. Acute suicide risk based on clinical judgement or a suicide attempt (as defined by the C-SSRS) within the past one year 9. Any history of ECT (greater than 8 sessions) without meeting responder criteria 10. Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT) 11. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma 12. Untreated or insufficiently treated endocrine disorder. 13. Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion) 14. Contraindication to MRI (ferromagnetic metal in their body) 15. Treatment with an investigational drug or other intervention within the study period 16. Depth-adjusted aiTBS treatment dose \> 65% maximum stimulator output (MSO) 17. Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score. 18. Any other condition deemed by the PD to interfere with the study or increase risk to the participant

Inclusion Criteria: * 18 years of age or older * Scheduled Heartmate 3 ® dLVAD implantation Exclusion Criteria: * \<18 years of age * Scheduled for dLVAD that is NOT a Heartmate 3 (R) device