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Inclusion Criteria: 1. Women who present to receive a screening mammogram. 2. Women of all races, ethnicities, and socio-economic backgrounds. 3. Signed informed consent obtained prior to any study assessments and procedures. 4. Age 30-75 years of age and female. Exclusion Criteria: 1. Women with findings that are \< 0.5 cm or \> 3.5 cm 2. Palpable lesion (to the participant) 3. Positive clinical findings that cause a visible and obvious deformity of the breast or alteration in the skin appearance of the breast. 4. Women with breast tenderness significant enough to prevent completion of any of the study examinations. (Both ultrasound and Bexa require a light degree of pressure on the breast; certain women, very few, have enough breast tenderness that they cannot tolerate the pressure of either Bexa or ultrasound. Mammograms exert substantially more pressure on the breast.) 5. Women with breast significant skin scarring enough to prevent effective BBE (e.g., keloid scarring of the breast, for example), because extensive, hard surface scarring introduces artifact in the Bexa exam. Participant exclusion will be determined by the Bexa examiner. 6. Greater than 3 positive findings in a given breast. 7. Women who are unable to comprehend or unwilling to sign an informed consent form. 8. Women ages \< 30 and \> 75 years of age. 9. Pregnant women. 10. Women who have had a mastectomy - unilateral or bilateral. 11. Women who have had a recent (past 30 days) biopsy performed. 12. Women who have had a prior history of breast cancer in either breast. 13. Women who have had radiation to the breast. 14. Women who have had any breast surgery within the last 12 months.

Inclusion Criteria: * Female over the age of 18 * Preoperative pathologically confirmed invasive breast cancer or ductal carcinoma in situ * Clinical classification T1, T2 (maximum tumor diameter ≤5cm) * Single-center tumor (preoperative confirmation by B-ultrasound, MRI and other imaging examinations) * No clinical or imaging evidence of distant metastasis * Able and willing to sign informed consent Exclusion Criteria: * Tumor in the lower inner quadrant * Tumor in multiple quadrants * Imaging or intraoperative pathology indicates tumor invasion of the nipple areola, skin, or pectoralis major * Locally advanced breast cancer patients are undergoing neoadjuvant therapy * Tumor in multiple quadrants * Have been participating in other clinical trials, which may affect the participation in this trial * Previous history of breast cancer (patients with recurrence after ipilateral breast-conserving surgery) * Pregnant and lactating women * Patients with severe cardiopulmonary disease or severely impaired lung function are not suitable for surgical establishment of an air cavity

Inclusion Criteria: * A confirmed diagnosis of severe or uncontrolled asthma under the care of the Manchester or Liverpool severe asthma services * Participants aged 16-25 years. * Informed consent provided. Exclusion Criteria: * Inability to provide informed consent. * Participants with additional long-term conditions who identify their dominant health concern to be non-asthma related. * Focus group only- inability to converse in English

Inclusion Criteria: * Type 2 diabetes mellitus (diagnosed by the physician) * Score \>3 on Michigan Neuropathy Screening Instrument-Questionnaire and score \>2 on MNSI-Physical Examination * Diabetic peripheral neuropathy symptoms below the ankle (numbness, tingling, burning, sharp pain, increased sensitivity, etc.) Exclusion Criteria: * Presence of any other systemic disease rather than diabetes such as end-stage renal failure, uncontrolled hypertension, severe dyslipidemia, chronic liver disease, autoimmune disease, advanced chronic obstructive pulmonary disease, etc. * Diabetic ulcer in either foot * Total or partial amputation of lower extremities * Active inflammations or other inflammatory neuropathies including chronic inflammatory demyelinating polyneuropathy, proximal diabetic neuropathy, chemotherapy-induced peripheral neuropathy, autonomic neuropathies, or other neuropathies not associated with DM such as B12 deficiency * History of fracture, strain, history of trauma leading to nerve injuries in the last year.

Inclusion Criteria: * Having signed the written Informed Consent Form (ICF); * Male or female aged ≥18 years; * Life expectancy ≥12 weeks; * Eastern Cooperative Oncology Group (ECOG) Performance Score 0 or 1; * Patients with histologically or cytologically confirmed locally advanced or metastatic breast cancer, ovarian cancer, prostate cancer or other advanced solid tumors who have experienced disease progression, and available SOC therapies had been exhausted; * be willing to provide tumor tissue samples (fresh frozen \[SF\] or previously retained paraffin-embedded \[FFPE\] tumor tissue samples) or peripheral blood germline DNA or ctDNA sample to detect BRCA mutation, or other deficiency in the HR pathway (by the detection method of next generation sequencing \[NGS\]) * At least one measurable lesion according to RECIST v1.1; * No serious hematological, cardiopulmonary, or liver or kidney diseases other than the primary disease; * Adequate organ function and bone marrow function. Exclusion Criteria: * Previous or current use of POLQ inhibitors; * Hypersensitivity to the active pharmaceutical ingredient or any excipient of SYN818; * Central nervous system (CNS) metastasis or meningeal metastasis with clinical symptoms, or other evidence indicating that CNS metastasis or meningeal metastasis has not been adequately controlled; * Other malignant tumors than the study tumors within 5 years prior to the first dose of the study drug, except for localized cancers that have been evidently cured or disease-free for at least 3 years, such as basal or squamous cell skin cancer, superficial bladder cancer, prostate carcinoma in situ, carcinoma in situ of cervix, or carcinoma in situ of breast; * Patients with Myelodysplastic syndrome (MDS)/Acute myeloid leukemia (AML) or with features suggestive of MDS/AML; * Dysphagia or refractory nausea and vomiting, malabsorption, extracorporeal biliary shunts, or gastrointestinal disorders that affect drug absorption, e.g., Crohn's disease, ulcerative colitis, or short bowel syndrome, or other malabsorption conditions; * Major surgery or serious trauma within 4 weeks prior to the first dose of the study treatment or major surgery planned during the trial period, and none of the AEs related to surgery or major trauma have resolved (to ≤ CTCAE v5.0 Grade 1 or baseline level) before the first dose of the study drug; * History of use within 2 weeks prior to the first dose of the study treatment and need to use protocol-prohibited potent inhibitors or potent inducers of cytochrome P450 (CYP) 3A4/BCRP/P-gp during the study; * Serious systemic diseases or laboratory abnormalities or other conditions that, at the Investigator's discretion, will make it unsuitable for the patient to participate in this clinical trial.

Inclusion Criteria: All adult patients with available records in the western region of Saudi Arabia Exclusion Criteria: age below 18 years

Inclusion Criteria: To be eligible to participate in this study, an individual must meet all of the following criteria: * have Venezuelan nationality * have arrived in Lima in years 2014 to the present * be 18 years of age or older In addition, in order to be eligible to participate in this study, an individual must meet one of the following criteria: * score 10 points or more at the Patient Health Questionnaire (PHQ-9) or * score 10 points or more at the General Anxiety Disorder (GAD-7) or * have a history of trauma exposure as listed in the Life Events Checklist (LEC-5) and score 31 points or more in the PTSD Checklist (PCL-5) Exclusion Criteria: An individual is excluded from the study if they respond positively to one or more of the following questions during screening: * Suicidal ideation: "When someone feels as upset as you do, they may have thoughts that life isn't worth living. What thoughts have you had like this?" * Homicidal ideation: "When someone feels as upset as you do, they may have thoughts about hurting the person who has upset or hurt them. What thoughts have you had like this?" * Psychosis: "Do you have a diagnosis of psychosis or schizophrenia?"

Inclusion Criteria: * Acute stroke Exclusion Criteria: * Traumatic intracranial bleeding without stroke * A malign, aggressive disease * Severe aphasia or incapable of independent decision making

Inclusion Criteria: * being an adult aged 18 or above with a family member aged 60 or above requiring caregiving, providing at least 6 hours of care per week * self-identifying as a family caregiver * living in Hong Kong * able to communicate with the interventionist * voluntary participation * reporting mild risk need in Carer Need Screening tool Exclusion Criteria: * having diagnosed Alzheimer's or other dementia * experiencing acute health conditions that hinder caregiving support or intervention participation

Key Inclusion Criteria: * Participant has advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy. * Presence of genetic alterations in PIK3CA/AKT1/PTEN in participants' tumor tissue. * Participant must have received at least 1 prior line of endocrine therapy for advanced/metastatic disease or participant who has radiological evidence of breast cancer recurrence or progression during or within 12 months from the end of adjuvant treatment with endocrine therapy, as these participants are considered as first-line relapsed participants. * Progression on previous cyclin-dependent kinase 4 and 6 inhibitor treatment in combination with fulvestrant or aromatase inhibitor is required. Key Exclusion Criteria: * Active or newly diagnosed central nervous system metastases. * Participants with advanced, symptomatic visceral spread, who are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver involvement \>50%. * Participants with any toxicities related to prior radiation therapy that have not resolved to baseline or to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 Grade ≤1, except alopecia and peripheral sensory neuropathy (Grade ≤2). Note: Other inclusion/exclusion criteria may apply.

Inclusion Criteria: * African American or Hispanic persons ≥ 40 years old * Non-Hispanic white persons ≥ 50 years old * Anyone ≥ 18 years old with diabetes type 1 or type 2 * Anyone ≥ 18 years old who already has a glaucoma associated disease * Anyone ≥ 18 years old with a family history of glaucoma Exclusion Criteria: * Declines to sign written informed consent * Cannot communicate in English

Inclusion Criteria: * Histologically confirmed breast cancer, completely excised * Natural or iatrogenic menopausal status * No evidence of distant metastasis * Self-identified moderate to severe symptoms of genitourinary syndrome * Normal kidney and liver function * Written Informed Consent signed and dated by patient * Negative Papanicolau (Pap) Smear Cytology Test within 1 year prior to enrollment Exclusion Criteria: * Vaginal or uterine bleeding of unknown origin * Current diagnosis of any non-breast malignancy * Metastatic disease * Currently on chemiotherapy * Currently on treatment with tamoxifen * Mentally incompetent or evidence of active substance or alcohol abuse * Endometrial hyperplasia * Pregnancy or lactation * Currently use of other vaginal therapy for the same purpose (if present, they have to be stopped 15 days before baseline visit) * Clinically significant metabolic or endocrine disease not controlled by medication

Inclusion Criteria: * Meets the DSM-5 criteria for Major Depressive Disorder, with a current major depressive episode duration of \> 6 weeks and ≤ 18 months. * A score of ≤ 22 (midrange mild/moderate) on the Hamilton Anxiety Rating Scale. * Montgomery-Asberg Depression Rating Scale total score of \> 24 \[indicating moderate to severe depression\] at Screening and at Baseline. * Subject is compliantly using a single selective serotonin reuptake inhibitors / serotonin norepinephrine reuptake inhibitor antidepressant for at least 6 weeks for their current episode of depression, with an adequate dose, and with an inadequate response as defined by the Antidepressant Treatment Response Questionnaire. The dosage of the current antidepressant must have been stable for the past 4 weeks, and the dosage and specific antidepressant used should remain the same from Screening through the end of the Follow-up Period. Exclusion Criteria: Note: History implies lifetime history, unless otherwise specified * History of schizophrenia or other psychotic disorder, major depressive disorder with psychotic features or concomitant DSM-5 depressive disorders, bipolar I or II disorder, cyclothymic disorder, delirium, dementia, amnestic disorder, or cognitive disorder. * Current diagnosis or active symptoms within the last 2 years of obsessive-compulsive disorder, posttraumatic stress disorder, panic disorder, or eating disorder, according to DSM-5 criteria. * Primary diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder, according to DSM-5 criteria. Current or history within the last 2 years of self-injurious behavior is exclusionary. * Has failed more than 2 single selective serotonin reuptake inhibitors / serotonin norepinephrine reuptake inhibitor antidepressant treatments, including the current serotonin reuptake inhibitors / serotonin norepinephrine reuptake inhibitor, during the current depressive episode, despite an adequate dose (per Antidepressant Treatment Response Questionnaire) and duration (at least 6 weeks). * Failure to respond to triiodothyronine or thyroxine augmentation for the treatment of depression. * Started new psychotherapy or had a change in the intensity of psychotherapy within 8 weeks before Screening. * Is suicidal at Screening or Baseline * History or current evidence within previous 3 months before Screening of uncontrolled, clinically significant neurological, gastrointestinal, respiratory, renal, hepatic, immunological, hematological, or other medical disorder, including cancer, that would jeopardize the safe participation of the subject in the study (in the opinion of the Investigator). * History of thyroid disease * History of multiple endocrine neoplasia syndrome * Diagnosis of epilepsy or history of convulsions, including childhood febrile seizure. Use of co-administered drugs that may lower seizure threshold is excluded. * Females who are pregnant, intend to become pregnant or are breastfeeding. * Antidepressants: Prior use of psychedelics, ketamine, or esketamine, for the treatment of Major Depressive Disorder. * Antidepressants: Current use, or use within 4 weeks prior to Screening, of any other augmentation agents for Major Depressive Disorder (e.g. second-generation antipsychotics \[SGA\], monoamine oxidase inhibitors \[MAOI\], tricyclic antidepressants \[TCA\], lithium, or bupropion) * Current or prior use of treatment for hypothyroidism including but not limited to synthetic or natural thyroid hormone, triiodothyronine and/or thyroxine. * Concomitant use of biotin of any dose and in any preparation 14 days prior to Day 1 until after the last study visit at Week 8 (Day 56). * Medications that are strong cytochrome P450 3A4 inhibitors or strong cytochrome P450 3A4 inducers are not allowed. * Prescription drug/controlled substance abuse, or illicit substance use within 1 year of Screening or positive urine drug results at Screening or Baseline for an illicit substance. * History or presence of cataract on ophthalmic examination (including slit-lamp), glaucoma, inflammatory eye disease or prior ophthalmic surgical procedures or laser surgery in either eye

Inclusion Criteria: 1. Patients aged 18 and older. 2. Blood pressure measured at ≥140/80. 3. Diagnosis of essential hypertension. Exclusion Criteria: 1. Pregnant patients. 2. Individuals without a prior diagnosis of hypertension. 3. Patients with end-organ damage (hypertensive emergency). 4. Patients whose routine antihypertensive agents are unavailable. 5. Patients who leave the clinic without permission, making follow-up data inaccessible.

Inclusion Criteria: * Age ≥ 18 years. * All biopsy-confirmed invasive ductal, invasive lobular and other rare histologic types of carcinoma. * Patients with early stage Breast cancer, or LABC ; i.e., Stage IIA - IIIC cancers (T2 N0 M0 to Any T, N3, M0) or Stage IV (Any T, Any N, M1) per AJCC guidelines (8th Edition). * Assessed as indicated, by a multidisciplinary team of treating medical, surgical and radiation oncologist and found suitable for radiation treatment. * Patient referred for standard palliative radiotherapy or curative radiotherapy, which may include (but are not limited to) any of the following dose regimens: 1) 5-8 Gy in one fraction, 2) 20 Gy in 5 fractions, 3) 30 Gy in 5 fractions, 4) 35 Gy in 5 fractions, 5) 30 Gy in 10 fractions, 6) 40 Gy in 10 fractions, 5) 50 Gy in 20 fractions, 6) 60 Gy in 30 fractions and 7) 66 Gy in 33 fractions, or radiobiologically similar doses. * Able to understand and give informed consent. * Weight \< 140 kg. * Target lesion accessible for MRg-FUS+MB procedure. * Able to communicate sensation during the procedure. * Creatinine within normal institutional limits or creatinine clearance \>60mL/min/ Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients with Chest-Wall and Locally Advanced Breast Cancer. 1.73m2 for patients with creatinine levels above institutional upper limit of normal. Exclusion Criteria: * Pregnant or lactating women may not participate due to the embryotoxic effects of protocol treatment. * Unable to have a contrast-enhanced MRI scan - standard of care criteria. * Patients having received anthracycline or taxane based chemotherapy within the past 5 days. * Patients with metallic or breast implants. * Subjects with connective tissue disorder, musculoskeletal deformity. * Target lesion causing deep ulceration, bleeding or discharge of the overlying skin. * A fibrotic scar along the proposed FUS beam path. * Severe cardiovascular, neurological, renal or hematological chronic disease. * Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 3. * Any condition that in the investigator's opinion precludes participation. * Unable to tolerate required stationary position during treatment. * Allergy to Definity microbubbles. * Cardiac disease or unstable hemodynamics including myocardial infarction within six months, unstable angina, congestive heart failure, cardiac shunts, cardiac arrhythmia and cardiac pacemaker. * Contraindication to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation like cisapride, erythromycin, tricyclic antidepressants, Class IA and III antiarrhythmic agents and some antipsychotics like haloperidol, droperidol, quetiapine, thioridazine, ziprasidone. * Known QT prolongation = (QTc \> 450ms for men or \>470ms for women) with cardiac impairment if ECG is requested as per SOC. * History of bleeding disorder, coagulopathy. * Severely impaired renal function with estimated glomerular filtration rate \< 30ml/min/1.73m2 and/or on dialysis.

Inclusion Criteria: \- 1\. For premenopausal or postmenopausal women, the definition of menopause: 1. previous bilateral oophorectomy, or age ≥60 years; or 2. Age \<60, natural postmenopausal status (defined as spontaneous cessation of regular menstruation for at least 12 consecutive months without other pathological or physiological causes), E2 and FSH at postmenopausal levels; 2. All patients had estrogen receptor (ER) positive (\> 10%), HER2 receptor-negative invasive breast cancer regardless of PR expression level. Follow the 2018 ASC-CAP HER2 Negative Interpretation Guidelines. Immunohistochemical (IHC) scores of 0+ or 2+ and in situ hybridization (ISH) test negative were confirmed by pathology laboratory (HER-2/CEP17 ratio \< 2.0); 3. Patients with initial treatment of stage II-III whose tumor stage meets AJCC 8th edition standard; 4. There is no known severe hypersensitivity to compounds or endocrine therapy similar to Darcilil or darcilil excipients. 5\. ECOG 0-1; 6. The patient must be able to swallow oral medications. 7. The functional level of the organ must meet the following requirements: 1. Bone marrow function ANC ≥ 1.5×109/L (no growth factor used within 14 days); PLT ≥ 100×109/L (no corrective therapy used within 7 days); Hb ≥ 100 g/L (no corrective therapy used within 7 days); 2. Liver and kidney function TBIL≤1.5×ULN; ALT and AST≤3×ULN (ALT and AST≤5×ULN in patients with liver metastasis); BUN and Cr≤1.5×ULN and creatinine clearance ≥50 mL/min (Cockcroft-Gault formula); 3. 12-lead electrocardiogram QT interval ≤480 ms; 8. Able to accept all needle biopsies required by the protocol; 9. Voluntarily participate in this study, sign informed consent, have good compliance and be willing to cooperate with follow-up. Exclusion Criteria: 1. Previously received any form of anti-tumor therapy (chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.); 2. At the same time receive any anti-tumor treatment other than that prescribed in other protocols; 3. Bilateral breast cancer, inflammatory breast cancer or ocessive breast cancer; 4. Stage IV breast cancer; 5. Other malignant tumors have appeared in the past 5 years; 6. Severe heart, liver, kidney and other vital organ dysfunction; 7. Inability to swallow, chronic diarrhea, and intestinal obstruction, with multiple factors affecting drug use and absorption; 8. Known allergic history of the drug components of this protocol; Have a history of immunodeficiency, including HIV positive, HCV, active viral hepatitis B or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation; 9. Pregnant and lactating women, fertile women who tested positive for baseline pregnancy tests, or women of childbearing age who were unwilling to take effective contraceptive measures during the entire test period; 10. Concomitant diseases (including but not limited to severe high blood pressure, severe diabetes, active infection, etc.) that, in the judgment of the investigator, seriously endanger the patient's safety or affect the patient's ability to complete the study; 11. Have a clear history of neurological or mental disorders, including epilepsy or dementia. The investigator did not consider the patient suitable for participation in any other condition of the study.

Inclusion Criteria: 1. Age 18 and above 2. Hypertensive crisis (systolic ≥180 and/or diastolic ≥110 mmHg) Exclusion Criteria: 1. Patients presenting with hypertensive emergency (those with end-organ damage) 2. Patients who have traveled to another city or district within the last 4 days 3. Pregnant patients

Inclusion Criteria: Age: 18-60 years BMI: 18-28 kg/m² Weight: ≥ 50 kg T1DM Participants: Duration of T1DM: 1-30 years HbA1c: 5.7-7.5% Insulin Therapy: Using automated insulin delivery GCK-MODY Participants: HbA1c: 5.7-7.5% Genetic Confirmation: Positive GCK sequencing Control Participants: HbA1c: less than 5.5% \*\* Exclusion Criteria: Severe Hypoglycemia: ≥1 episode in the past 3 months Comorbidities: * Any hospital admissions for diabetic ketoacidosis in the past 6 months * SBP greater than 140 mmHg and DBP greater than 100 mmHg * eGFR by MDRD equation of less than 60 mL/min/1.73 m² * AST or ALT greater than 2.5 times ULN * Hct less than 35% Medications: * Any antioxidant vitamin supplement within 2 weeks before the study * Any systemic glucocorticoid * Antipsychotics * Atenolol, Metoprolol, Propranolol * Niacin * Any thiazide diuretic * Any oral contraceptive pill with greater than 35 mcg ethinyl estradiol * Growth hormone * Any immunosuppressant * Antihypertensive * Any antihyperlipidemic Other: * Pregnancy * Tanner stage less than 5 * Peri- or post-menopausal women * Active smoker T1DM Participants: Medications: Any diabetes medication except insulin C-peptide: greater than 0.7 ng/mL (fasting) GCK-MODY Participants: None specific

Inclusion Criteria: * Age ≥18 years * Invasive ER+ breast cancer * No diabetes treatment * Planned for initiation of any adjuvant endocrine therapy. Exclusion Criteria: * Pregnancy or lactation, * Psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule; these conditions will be discussed with the patient before registration in the trial.

Inclusion Criteria 1. 50 years of age and older 2. Admitted to the intensive care for greater \> 48 hours 3. Able to understand and provide informed consent 4. Elevated depressive symptoms, defined as Screening PHQ-9 or PHQ-8 ≥ 10 or Screening PHQ-9 or PHQ-8 = 5-9 with the presence a core symptom of anhedonia (PHQ-9 or PHQ-8 Item 1) or depressed mood (PHQ-9 or PHQ-8 Item 2) 5. Willing to participate in cognitive testing 6. Access to a telephone 7. Discharge to home or an independent or assisted living facility 8. Response is a 1,2, or 3 on PHQ-9 or PHQ-8 item 7, answered yes to "Have you experienced a change in your memory or other aspect of thinking in the past 1 to 3 years?", or score in the 25% percentile or lower on the Montreal Cognitive Assessment (MOCA) based on normative data which account for age, gender, race, ethnicity and education. Exclusion Criteria: 1. Diagnosis of dementia or neurodegenerative disease (e.g. Alzheimer's disease, vascular dementia as per EHR and IQCODE, or Parkinson's disease) or on anti-dementia medications prior to ICU stay 2. Diagnosis of severe mental illness (bipolar disorder, schizophrenia, schizoaffective) as per EHR and screening questions 3. Persistent psychotic symptoms after ICU stay which would interfere with successful completion of intervention 4. Recent or recurrent alcohol or substance use disorder as per HER and Drug Abuse Screening Test 5. Life expectancy less than 1 year (e.g. terminal cancer diagnosis, discharged on hospice) 6. Ischemic or hemorrhagic stroke, traumatic brain injury, or undergoing neurosurgery prior, during or after ICU stay 7. Uncorrected visual or auditory impairment including legal blindness or deaf 8. Status post tracheostomy and not able to communicate 9. Incarcerated or on parole after ICU stay