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Inclusion Criteria: * Clinical criteria for ALS (Brooks et al., 2000; de Carvalho M., 2008), FTD (GornoTempini et al., 2011; Rascovsky et al., 2011) Exclusion Criteria: * na

Inclusion Criteria: * aged ≥45 years * poorly controlled DM (pDM), defined as HbA1c ≥9% within the preceding year Exclusion Criteria: * active TB * immunocompromise (use of immunosuppressors * current pregnancy

Inclusion Criteria: * Male or female, age reach and over 18 years at the time of signing informed consent, * Body mass index (BMI) between 18.0 and 35.0 kg/m\^2 (both inclusive), * Type 2 diabetes mellitus (as diagnosed clinically) before screening. * hemoglobin A1c of 7.5 - 9.0% (both inclusive) as assessed by central laboratory on the day of screening, * Treated with stable doses of oral antidiabetic drugs (OADs) , insulin or glucagon-like peptide-1 (GLP-1) receptor agonists (exenatide, liraglutide, etc.) within 3 months prior to screening; Exclusion Criteria: * Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method, * Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or systemic corticosteroids), * Any episodes (as declared by the participant or in the medical records) of diabetic ketoacidosis within 90 days before screening, * Presence or history of pancreatitis (acute or chronic) within 180 days before screening, * Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening. Chronic heart failure classified as being in New York Heart Association Class IV at screening, * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before screening or in the period between screening and randomisation. Pharmacological pupil dilation is a requirement unless using a digital fundus photography camera specified for non dilated examination.

Inclusion Criteria for All the Participants: * With confirmed pathological diagnosis and molecular subtyping results * Ability to provide a written informed consent Exclusion Criteria for Cancer Arm Participants: * Patients with a history of or currently suffering from other malignancies * Pregnant or planning to become pregnant female patients * Patients who have received cancer treatment, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, before blood draw * Patients with a history of blood transfusion within the past month * Patients with a known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation * Patients with persistent fever or undergoing anti-inflammatory treatment within 14 days before blood draw * Any other conditions that the researcher deems may make the patient unsuitable for inclusion in the study or may interfere with the completion of the study * Patients in poor physical condition who are not suitable for blood draw * Patients who cannot provide informed consent or refuse blood draw Exclusion Criteria for Benign Diseases Arm Participants: * History of malignancies * Current malignancies or precancerous lesions

3.1 Inclusion Criteria Patients must meet all of the following criteria to be eligible: Age: ≥18 years old. Clinical-pathological confirmation: cT2-cT4 breast cancer, or cT1c with axillary lymph node metastasis. Histopathologically confirmed HR+/HER2- invasive breast cancer: ER and/or PR positive (IHC nuclear staining ≥1%). HER2-negative (IHC 0 or 1+ without FISH testing, or IHC 2+ with FISH-negative amplification). Ki67 ≥20%. Clinically measurable lesions: Measurable lesions confirmed by ultrasound, mammography, or MRI (optional) within 1 month prior to randomization. Adequate organ and bone marrow function (within 1 month prior to chemotherapy): Absolute neutrophil count (ANC) ≥2.0 × 10\^9/L. Hemoglobin ≥90 g/L. Platelet count ≥100 × 10\^9/L. Total bilirubin \<1.5 × ULN (upper limit of normal). Creatinine \<1.5 × ULN. AST/ALT \<1.5 × ULN. Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% by echocardiography. Reproductive status: Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization. ECOG performance status: ≤1. Informed consent: Signed written informed consent. 3.2 Exclusion Criteria Patients meeting any of the following criteria will be excluded: Evidence of metastatic breast cancer: Chest/abdominal CT and bone scan required at any time from diagnosis to randomization to exclude metastasis. PET/CT may substitute for other imaging modalities. Prior systemic therapy: Chemotherapy, endocrine therapy, targeted therapy, or radiotherapy for the current breast cancer. Second primary malignancy, except: Adequately treated non-melanoma skin cancer. Prior immunotherapy: Treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or other immune checkpoint inhibitors. Immune-related conditions: Diagnosed immunodeficiency or active autoimmune disease. Severe cardiopulmonary disease: Uncontrolled or clinically significant. Active hepatitis: Hepatitis B or C with detectable viral load. Transplant history: Prior organ or bone marrow transplantation. Pregnancy or lactation: Pregnant or breastfeeding women. Other contraindications: Severe uncontrolled comorbidities deemed by investigators to contraindicate chemotherapy or PD-1 inhibitor therapy.

Inclusion Criteria: * Age 18 - 69 years * Medical diagnosis of a depressive disorder, including depressive adjustment disorder and depressive episodes in the context of bipolar disorder, i.e. one of the following ICD-10 codes: * F32 Depressive Episode * F33 Recurrent Depressive Disorder * F31.3 Bipolar Affective Disorder, current mild or moderate depressive episode * F31.4 Bipolar Affective Disorder, current severe depressive episode without psychotic symptoms * F43.20 Adjustment Disorder with Brief Depressive Reaction * F43.21 Adjustment Disorder with Prolonged Depressive Reaction * Inpatient admission * Written informed consent Exclusion Criteria: * Inability to fill out questionnaires with or without assistance due to language, physical, or cognitive limitations * Acute psychotic state * Known body schema disorders, e.g. due to significant neurological or malignant diseases, eating disorders, congenital or acquired physical limitations such as the absence of a body part * Deafness, blindness

Inclusion Criteria: 1. Diagnosis of type 2 diabetes mellitus. 2. Age between 18-75 years. 3. BMI ≥25 kg/m². 4. HbA1c \< 9%. 5. Stable dose of metformin for at least three months prior to enrollment. Exclusion Criteria: 1. Use of antidiabetic drugs other than metformin within three months prior to enrollment. 2. History of ketoacidosis or severe hypoglycemia within six months prior to enrollment. 3. Significant renal or hepatic impairment (eGFR \<60 mL/min/1.73 m²; ALT/AST \>2× ULN). 4. Pregnancy or lactation.

Inclusion Criteria: 1. Female patients aged ≥18 years and ≤75 years who have not received prior treatment; 2. ECOG score of 0 to 1; 3. Her-2 (0), Her-2 (1+), Her-2 (2+) must test negative by ISH (in situ hybridization). 4. Hormone receptor status: ER (Estrogen Receptor) \<1%, PR (Progesterone Receptor) \<1%; 5. The functional levels of major organs must meet the following requirements (no blood transfusion within 2 weeks prior to screening, no use of white blood cell or platelet-raising drugs): 6. Complete blood count： Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelet count (PLT) ≥90×10\^9/L; Hemoglobin (Hb) ≥90 g/L; 7. Blood chemistry Total bilirubin (TBIL) ≤ upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×ULN; Alkaline phosphatase ≤2.5×ULN; Blood urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN; 8. Echocardiogram Left ventricular ejection fraction (LVEF) ≥55%; 9、12-lead ECG QTc interval corrected by Fridericia's method (QTcF) \<470 msec. 10、For premenopausal or surgically unsterilized female patients: agree to abstain from sexual intercourse or use effective contraceptive methods during the treatment period and for at least 7 months after the last administration of study treatment. 11、Voluntarily participate in this study, sign the informed consent form, have good compliance, and are willing to cooperate with follow-up visits Exclusion Criteria: 1. Stage IV (metastatic) breast cancer; 2. Inflammatory breast cancer; 3. A history of receiving anti-cancer treatment or radiotherapy for any malignant tumor, excluding curative treatments for in situ cervical cancer, basal cell carcinoma, or squamous cell carcinoma, etc.; 4. Concurrently participating in other clinical trials involving anti-cancer therapies, including endocrine therapy, bisphosphonate therapy, or immunotherapy; 5. Having undergone significant non-breast cancer related surgical procedures within 4 weeks prior to enrollment, or not having fully recovered from such procedures; 6. Severe cardiac disease or conditions, including but not limited to the following: * A confirmed history of heart failure or systolic dysfunction (LVEF \<50%); * High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate \>100 bpm, significant ventricular arrhythmias (e.g., ventricular tachycardia), or higher-grade atrioventricular block (i.e., Mobitz Type II second-degree atrioventricular block or third-degree atrioventricular block); * Angina requiring anti-anginal medication; * Clinically significant valvular heart disease; * ECG showing transmural myocardial infarction; * Poorly controlled hypertension (systolic blood pressure \>180 mmHg and/or diastolic blood pressure \>100 mmHg); 7. Inability to swallow, intestinal obstruction, or other factors affecting drug intake and absorption; 8. Known history of allergies to the components of the study medication: a history of immunodeficiency, including positive HIV tests, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 9. Pregnant or nursing women, women of childbearing potential with a positive baseline pregnancy test, or women of reproductive age who are unwilling to use effective contraceptive measures throughout the trial period and for 7 months after the last administration of study medication; 10. Having severe concomitant diseases or other conditions that would interfere with planned treatment, or any other circumstances deemed by the investigator to make the patient unsuitable for participation in this study.

Inclusion Criteria: * Youth and young adults 11-25 years of age * MS diagnosis or clinically isolated syndrome per revised McDonald diagnostic criteria and International Pediatric MS Study Group Criteria * A score of 10 or above on the CES-DC scale. Exclusion Criteria: * Have non-specific white matter abnormalities and metabolic or infectious etiologies for white matter abnormalities * Do not speak and read English at a level needed to complete the questionnaires (4th grade level) * Have significant motor disability (EDSS ≥4) * Are at increased risk of cardiac or other complications of exercise testing, as determined by the pediatric neurologist or physician

Inclusion Criteria: Samples from patients with group 1, 3 or 4 PH stored in the Spanish PH Biobank (IdiBAPS). A maximum of 100 samples was limited for PAH associated to groups 1.1, 1.2 and 1.3 (idiopathic, heritable and drug-induced PH) and 100 samples from group 4. Samples will be randomly selected by the Biobank managers. All available samples from control (matched for sex and age) and group 3 PH. Exclusion Criteria: 1. Samples from PAH associated to HIV infection, schistosomiasis or PAH with features of venous/capillary (PVOD/PCH) involvement. 2. Samples from patients that were analyzed in our previous study (PMID: 32041235)

Inclusion Criteria * Each participant must meet the following criteria to be enrolled in this study: * Adults aged 18 to 75 years. * WHO functional class I, II/III despite treatment with maximally tolerated doses of 2 or more treatment modalities including PDE5 inhibitors, guanylate cyclase stimulators, endothelin receptor antagonists, and prostanoids when appropriate. Exclusion Criteria * Participants who meet any of the following criteria will be excluded from the study. * Participants with serious concomitant morbidity per investigator assessment.

Inclusion Criteria: * Aged between 18 and 75 years old. * Diagnosed with hypertension, based on ICD-9 codes (401-401.9). * Independent in performing activities of daily living. * Ability to respond to SMS messages. Exclusion Criteria: * Diagnosis of Parkinson's disease. * Refusal to sign the informed consent form. * Diagnosis of cancer. * Mobility limitations that prevent engaging in physical activity. * Lack of a smartphone with internet access.

Inclusion Criteria: * Non-insulin treated T2D diagnosis (not treated at all or only with metformin); * Physically inactive (less than 150 minutes/week of moderate physical activity); * Age between 40 and 70; * HbA1c below 8.5%. Exclusion Criteria: * Diabetes diagnosis less than 3 years before the study initiation; * Pregnancy; * Symptomatic heart disease, e.g. history of myocardial infarction, coronary bypass, stenting procedure, angina, or any ischemic cerebrovascular event; * Use of a medication that significantly impacts glucose metabolism (oral steroids); * Use of a medication that significantly lowers heart rate (beta blockers, reserpine, guanethidine, methyldopa, clonidine, cimetidine, digitalis, calcium channel blockers, amiodarone, antiarrhythmic drugs, or lithium); * Atrial fibrillation; * Use of an electronic pacemaker.

Inclusion Criteria: * Onset of stroke \<6 months ago, or \>6 months since the last stroke event; * Age \>=18 years and \<85 years (as the probability of Vascular Cognitive Impairment increases above 85); * Patients with damage in the middle cerebral artery territory; * NIHSS \>4 and \<26; * mRS score \>=2; * Completion of CT or MRI; * No neurological or psychiatric disorders; no impairment of consciousness; able to comply with relevant treatments; no severe cognitive dysfunction (MMSE \>=15); * All participants are right-handed; Sign the informed consent form. Exclusion Criteria: * History of epilepsy or psychiatric disorders (including depression, anxiety, or schizophrenia); * Severe comorbidities; * History of medication use: benzodiazepines, baclofen, antidepressants; * Non-compliance with the treatment plan; * Acute-phase cerebral hemorrhage, acute infectious diseases; * Severe suicidal tendencies in individuals with depression; * Individuals suffering from severe headaches, high blood pressure, malignant tumors, open wounds, vascular embolism, leukopenia, etc.; * Severe alcohol abuse; * History of cranial surgery, individuals with metal implants in the brain; * Individuals with an implanted cardiac pacemaker; * NIHSS \>26, MMSE \<15; * Any disease likely to prevent the patient from surviving more than one month; * Pregnant individuals.

Inclusion Criteria: 1. . Age ≥ 18 years 2. PS ECOG 0-1 3. Histologically confirmed early breast carcinoma with positivity for hormone receptors (ER+ IHC \>10%) and HER2 negative (IHC value 0 1+ and/or FISH not-amplified) 4. Primary resective surgery for early breast cancer with adequate assessment of lymph node status (sentinel lymph node biopsy or complete axillary dissection), with one of the following diagnostic stages: * T1-3, N0, M0 * T1-3, pN1mic, M0 * T1-3, pN1a, M0 5. Indication for adjuvant treatment with endocrine therapy (ET) or chemo endocrine therapy (CET), according to the decision of the reference Breast Unit 6. Meeting the criteria for "intermediate" risk, i.e., no "low" or "high" risk of recurrence, as defined in the ministerial decree of 18/05/21: * Low risk defined by at least 5 of the following: G1, T1a-b, KI67 \< 15, N neg, ER \> 80% * High risk, defined by at least 4 of the following: G3, T \> 2, Ki67 \> 30, N pos, ER \< 30% 7. Indication for genomic test (Oncotype DX®, Mammaprint®, PAM50 Prosigna®, Breast Cancer Index®, EndoPredict®) by the Breast Unit 8. Ability to provide written informed consent to participate in the registry study, approved by the local Ethics Committee. 9. The patient underwent genomic testing starting from September 2021 Exclusion Criteria: 1. Low-risk and High-risk patients as defined in the Ministerial Decree of 18/05/21 2. ER negative and/or HER2 positive tumours 3. More than 3 lymph nodes involved at clinical/pathological staging 4. Invasive tumours \<2mm evaluated by local pathologists 5. Previous history of breast cancer 6. Synchronous breast cancers 7. Multifocal tumours 8. Metastatic disease 9. Contraindications to adjuvant treatments 10. Performance status (PS ECOG) \> 1 and / or other clinical factors that would make the patient a candidate and unsuitable for systemic adjuvant treatment or have received an exclusive indication for precautionary hormone therapy as part of the Breast Unit collegial assessment. 11. Psychiatric diagnosis that may affect the ability to participate in this study

Inclusion Criteria: * Meets the diagnostic criteria for acute attack of asthma/AECOPD; * Age range from18 years to 80 years(asthma) and 40 yesrs to 80 years(COPD); * The investigators agreed to participate in this clinical study by voluntarily signing an informed consent form. Exclusion Criteria: * Patients with combined pulmonary abscess, pulmonary interstitial fibrosis, active pulmonary tuberculosis, bronchiectasis and other pulmonary diseases; * Patients with severe cardiovascular and cerebrovascular diseases (such as malignant arrhythmia, unstable angina pectoris, acute myocardial infarction, grade 3 or above cardiac function, stroke, cerebral hemorrhage, etc.); * Patients with severe liver diseases (such as liver cirrhosis, portal hypertension and bleeding caused by esophageal and gastric fundus varices) and severe kidney diseases (such as dialysis, kidney transplantation, etc.); * Patients with impaired consciousness or various mental disorders who are unable to communicate normally; * Pregnant and lactating women; * Those who are currently participating in other clinical trials within 1 month before enrollment; * Patients with contraindications to acupuncture (such as severe allergic or infectious skin diseases);

Eligibility Criteria: * Aged 18 years or older * Currently diagnosed with hypertension (either stage I or stage II hypertension) * Able to read/write/understand English * Have daily access to a smartphone * Engaged in hypertension care: Already been prescribed hypertension medication for a minimum of 6 months at the time of study enrollment * Demonstrated AH medication nonadherence by having over 73 days without documented AH medication prescription coverage (observable in Arizona Health Care Cost Containment System (AHCCCS) prescription drugs claims) in the past 12 months (i.e. \<80% mean adherence)

Inclusion Criteria: 1. Signed written informed consent obtained prior to entry in the study. 2. Scores below 15 on the Rosenberg Self-esteem Scale (RSE) 3. 18 years or older. Exclusion Criteria: 1. Psychosis 2. Bipolar type 1 3. Current suicide intent 4. PTSD 5. Cluster A or cluster B personality disorder 6. Substance dependence

Inclusion Criteria: * Histological diagnosis of iCCA (biopsy-proven tumor) * Either first diagnosis or post-resection recurrence (occurring ≥ 6 months after resection) * Unresectability assessment due to tumor location (leading to insufficient live remnant with/out implementation of hypertrophic parenchymal techniques) or underlying liver disease. Non-resectability assessed by an expert surgical team with experience on both resection and transplantation (centralized at INT Milan). * Age between 18 and 70 years * No macrovascular tumor invasion (NB: portal vein and/or hepatic vein occlusion from the external tumor compression and classified as "encasement" could be considered after expert radiology review) * No extrahepatic spread * Disease stability for at least 6 months * CA 19-9 \< 200 u/ml at transplant listing in absence of jaundice * No medical and surgical contraindications to liver transplantation * Good performance status, Eastern Cooperative Oncology Group (ECOG) 0 or 1 * No concomitant malignancies or history of other malignancies in the previous 5 years * Written informed consent Exclusion Criteria: * Hilar and distal cholangiocarcinoma * Progression of disease under chemotherapy +/- radiation therapy, assessed with either RECIST, mRECIST or Choi criteria * Evidence of lymph-nodal metastases * Evidence of extrahepatic disease * Prior extrahepatic metastatic disease * Concomitant malignancies or history of other malignancies in the previous 5 years * Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results * Any reason why, in the opinion of the investigator, the patient should not participate to the study

Inclusion Criteria: * Able to understand and voluntarily sign a written informed consent form. * Male or female aged 18-74 years (inclusive). * Meet the diagnostic criteria for type 2 diabetes mellitus (T2DM). * Have initiated treatment with any one of the SGLT2i monotherapy (dapagliflozin 10mg/d, canagliflozin 100mg/d, empagliflozin 10mg/d, ertugliflozin 5mg/day, or henagliflozin 10mg/day) for at least 8 weeks. * Have received 500-1000mg/day metformin treatment for at least 8 weeks with a stable, unchanged dose maintained during the screening period. * HbA1c level within the range of 7.5% to 9.5% inclusive. * Fasting blood glucose (FBG) level less than 15 mmol/L before randomization. * Body mass index (BMI) less than or equal to 40 kg/m2 before randomization. * Urine ketone test negative before randomization. * Estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73m2 or higher before randomization. * Agree to maintain the same diet and exercise habits throughout the trial, and be willing and able to correctly use a home blood glucose meter for self-monitoring of blood glucose (SMBG) and keep records. Exclusion Criteria: * Type 1 diabetes mellitus. * Various types of secondary diabetes. * Pending or having undergone pancreatic or β-cell transplantation. * History of pancreatitis or pancreatic resection. * Complicated with diabetic ketoacidosis or hyperosmolar coma. * Moderate or severe liver insufficiency of any cause, defined as ALT (SGPT), AST (SGOT), or alkaline phosphatase serum levels greater than 3 times the upper limit of normal (ULN) during the screening period. * Acute coronary syndrome (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, unstable angina), stroke, or transient ischemic attack (TIA) within the past 3 months. * Uncontrolled hypertension: systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 90 mmHg. * Hemoglobin level less than 10 g/l or 100 mg/dl. * Recurrent genitourinary infections more than twice within the past 3 months. * History of bariatric surgery or other gastrointestinal surgeries causing chronic malabsorption within the past 2 years. * Received anti-obesity medication within the past 3 months or any other treatment (e.g., surgery, radical diet plans) that led to unstable body weight at the time of screening. * History of cancer (except basal cell carcinoma) and/or cancer treatment within the past 5 years. * Human immunodeficiency virus (HIV) positivity. * Severe peripheral vascular disease. * Hematological malignancies or any diseases causing hemolysis or erythrocyte instability (e.g., malaria, babesiosis, hemolytic anemia). * Coexisting immune system diseases or currently receiving systemic corticosteroid therapy. * Changes in thyroid hormone dosage within the past 6 weeks, or any other uncontrolled endocrine or metabolic disorders outside of T2DM. * Alcohol or drug abuse within the past 3 months that may reduce trial compliance, or any chronic illnesses that the investigator believes may lead to reduced trial compliance or reduced use of the study drug. * Known allergies to components of the study medication or other drugs with similar chemical structures or excipients. * Pregnant women, women planning to become pregnant during the study, or lactating women. Subjects unwilling to use reliable contraception (including condoms, spermicides, or intrauterine devices) from the time of signing the informed consent form until 28 days after the last administration of the study medication, or women planning to use progesterone-containing contraceptives during this period. Men with fertility plans during the study. * Participation in any other clinical study within the past 30 days. * Any other condition deemed unsuitable for participation in this study by the investigator.