cyrilzakka/clinical-trials huggingface dataset:
Explore the Mechanisms Underlying Disease Resistance and Potential Primary Resistance Mechanism of Induction Therapy Lorlatinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harboring ALK Positive Mutation Revealed by Single-cell RNA Sequencing and Spatial Transcriptomics

This is an open-label, randomized, single-center study. This translational study aims to explore tumor microenvironment remodelling after induction therapy lorlatinib and identify mechanisms of disease persistence and potential primary resistance mechanisms of lorlatinib as induction therapy treatment in surgically resectable ALK-rearranged NSCLC by single-cell RNA sequencing (scRNA-seq) and Spatial transcriptomics.

to explore tumor microenvironment remodelling after induction therapy lorlatinib and identify mechanisms of disease persistence and potential primary resistance mechanisms of lorlatinib as induction therapy treatment in surgically resectable ALK-rearranged NSCLC by single-cell RNA sequencing (scRNA-seq) and Spatial transcriptomics.

Eligibility Criteria:
Inclusion Criteria:

* Male or female subjects who are ≥18 years of age；
* Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage IB-III) disease
* Clinical stage IIA/IIB/IIIA/IIIB assessed by EBUS-TBNA or PET(positron emission tomography)/CT can be resected.
* Documented ALK-fusion positive（ Ventana , assessed by a local laboratory）
* ECOG PS 0-1
* Performance status (ECOG) 0-1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing of lorlatinib
* Hematology , liver and kidney function are adequate for induction therapy .
* Cardiopulmonary function suitable for surgical treatment (ECG, echocardiography, pulmonary function or blood gas analysis).
* Be willing and able to provide written informed consent for the trial prior to any study specific procedures. The subject must also provide consent for correlative translational study.
* Female participants of childbearing potential must agree to use acceptable methods of contraception
* Male patients must be willing to use barrier contraception. Provide written informed consent.

Exclusion Criteria:

* Mixed squamous cell carcinoma, large cell carcinoma, small cell lung cancer.
* Prior treatment with any systemic anti-cancer therapy for NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug.
* Pregnant female patients; breastfeeding female patients.
* Malignancies other than the disease under study within 3 years prior to Cycle 1, Day 1, with the exception of patients with a negligible risk of metastasis or death and with expected curative outcome
* Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact participant safety
* Pregnant or lactating, or intending to become pregnant during the study Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
Connective Tissue Disease Patients With Pulmonary Hypertension

Adult patients with suspected or confirmed Connective Tissue Disease Patients (CTD)With Pulmonary Hypertension(PH)will be recruited. Patients will be approached, consented, have baseline demographics, diagnostics and disease activity measures recorded, and blood taken. The collection of data and biological material will mirror usual clinical practice as far as possible. Subjects will ideally attend further visits at 3, 6 and 12 months to have bloods taken, outcome measures recorded and questionnaires completed.


Eligibility Criteria:
Inclusion Criteria:

* Definite diagnosis of CTD included Systemic lupus erythematosus（SLE） diagnosed according to the 2019 The European Alliance of Associations for Rheumatology（EULAR） criteria, primary Sjogren's syndrome (pSS) defined according to the 2016 American College of Rheumatology(ACR) criteria, Systemic Sclerosis(SSc) defined according to the 2013 ACR criteria, mixed connective tissue disease (MCTD) defined by Sharp criteria, and Rheumatoid Arthritis(RA) defined according 2010 ACR criteria of two or more CTD at the same time were defined as having overlap syndrome (OS). Patients who had clinical and serological manifestations suggestive of systemic autoimmune diseases but did not fulfil the classification criteria for CTD were defined as having undifferentiated CTD (UCTD).
* PAH was diagnosed by right heart catheterization was defined as mean Pulmonary Artery Pressure (mPAP)\>20 Millimeters of mercury（mmHg）, Pulmonary Artery Wedge Pressure（PAWP）≤15mmHg, Pulmonary Vascular Resistance（PVR）\>2 Wood

Exclusion Criteria:

* significant interstitial lung disease or chronic obstructive pulmonary disease;
* left heart disease or congenital heart disease associated with pulmonary hypertension;
* chronic thromboembolic pulmonary hypertension;
* portal hypertension;
* drug or toxin exposure;
* HIV infection;
* any other diseases known to be associated with PAH;
* age\<18 years.
Clomiphene Citrate in Infertile Men With Idiopathic Oligoasthenozoospermia

The goal of this clinical trial is to learn if drug clomiphene citrate improves sperm parameters in infertile men with idiopathic oligoasthenozoospermia. It will also learn about the safety of clomiphene citrate. The main questions it aims to answer are:

* Does drug clomiphene citrate change sperm count and motility in infertile men with idiopathic oligoasthenozoospermia?
* What medical problems do participants have when taking drug clomiphene citrate? Researchers will compare drug clomiphene citrate to a placebo (a look-alike substance that contains no drug) to see if drug clomiphene citrate works to treat idiopathic oligoasthenozoospermia.


Eligibility Criteria:
Inclusion Criteria:

* Infertile men
* Idiopathic oligoasthenozoospermia (serum FSH and serum LH range was 2-7 IU/mL and serum testosterone level was \>300 ng/dl)

Exclusion Criteria:

* Azoospermia
* Body mass index \<18 kg/m2 and \>30 kg/m2
* Any abnormality on genital examination and scrotal sonogram
* History of genital diseases \& genital surgery
* Medical and endocrine disorders like uncontrolled diabetes mellitus, severe kidney disease and liver insufficiency
* Psycho-sexual abnormalities
* Antioxidant supplements in previous 3 months
* Smoking, drug, alcohol or substance abuse
* History of chemotherapy or radiotherapy
* Presence of any gross female factor abnormality
Can we Use Intravenous Injection of Tranexamic Acid in Routine Practice With Active Management of the Third Stage of Labor?

Obstetrical hemorrhage accounts for nearly one quarter of all maternal deaths worldwide and was the most common cause of maternal death in the Turkey \[1,2\]. Most of these deaths occur within 4 h of delivery and are a result of problems during third and fourth stages of labor. It also contributes significantly to serious maternal morbidity. Obstetric, surgical and radiological interventions play central role in the management of obstetric hemorrhage; however, pharmacologic management and in particular prohemostatic therapies also play an important role in the final maternal outcome. Administration of tranexamic acid (TA), intravenously in the third stage of labor may be one of these methods.

TA a synthetic derivate of the amino acid lysine, is an antifibrinolytic that reversibly inhibits the activation of plasminogen, thus inhibiting fibrinolysis and reducing bleeding. TA may enhance the effectiveness of the patient's own hemostatic mechanism \[3,4\]. In nonobstetric surgery, a systematic review of randomized controlled trails showed that tranexamic acid reduced the risk of blood transfusion \[ relative risk (RR) 0.61; 95% CI 0.54-0.69\] and also reduced the need for re-operation as a result of bleeding (RR 0.67; 95% CI 0.41-1.09). There was no evidence for an increased risk of thrombotic events \[5\].

In gynecology and obstetrics, TA is most commonly used to treat idiopathic menorrhagia, and is an effective and well-tolerated treatment when administered orally \[5,6,7\]. Bleeding associated with pregnancy (placental abruption, placenta previa) has also been treated with TA \[6\]. Furthermore, four randomized controlled studies have shown that TA reduces postpartum hemorrhage (PPH) following cesarean delivery \[7-11\]. Only one randomized trail is available evaluating the effect of TA use to prevent bleeding in the postpartum period following spontaneous vaginal delivery \[12\].

The purpose of our study was to estimate the effect of the addition of intravenous TA to a standard active management of the third stage of labor (which includes prophylactic injection of 10 IU of oxytocin within two minutes of birth, early clamping of the umbilical cord, and controlled cord traction).


Eligibility Criteria:
Inclusion Criteria:

* gestational age between 37 and 42 weeks,
* live fetus,
* cephalic presentation,
* vaginal birth.
* Patients who had a risk factors for PPH, such as multiple gestation, polyhydramnios, fetal macrosomia, antepartum hemorrhage, anemia (haemoglobin concentration \< 8 g/dL), severe pre-eclampsia, or coagulopathy

Exclusion Criteria:

* placenta previa,
* placental abruption,
* cesarean section or any uterine scar, abnormal placentation (accreta, increta, or percreta),
* a current or previous history of significant disease, including heart disease, liver, renal disorders.
Nasopharyngeal Carriage of S. Pneumoniae

This nasopharyngeal (NP) carriage surveillance study was requested by the European Agency for the Evaluation of Medicinal Products as a post-licensing commitment to determine whether the use of the pneumococcal conjugate vaccines (PCVs) including 7 then 13 valents (introduced in 2001 and 2010, respectively) caused a shift in the distribution of Streptococcus pneumoniae serotypes in children with acute otitis media and modified the resistance of this bacterial species to antibiotics.

Since September 2001, 121 pediatricians who are part of a research and teaching network (ACTIV) throughout France participated at this prospective study. From October to June of each subsequent year, children of both sexes suffering from suppurative acute otitis media (AOM) with fever and/or otalgia (in order to increase the probability of pneumococcal AOM), aged 6 to 24 months, were enrolled.

And a second group of healthy children aged 6 months to 15 years were also enrolled for the main study.

For ancillary study a subgroup of children were enrolled for assessment of E. coli (ESBL) resistance.

Eligibility Criteria:
Inclusion Criteria:

* both sexes
* suffering from suppurative AOM
* age: 6 months to 24 months for AOM
* age: 6 months to 15 years for healthy children
* informed consent from parents or guardians

Exclusion Criteria:

* Children with antibiotic treatment within 7 days before enrolment,
* severe underlying disease,
* inclusion in the study during the previous 12 months
Sex, Hormones and Gamma-Aminobutyric Acid (GABA) in Stress Induced Anhedonia in Depression

Using an innovative multi-modal imaging approach, this study investigates the role of the neurochemical gamma-aminobutyric acid (GABA), brain activity, as well as hormones in understanding sex differences in Major Depressive Disorder (MDD). Further, the investigators will link these markers to symptoms of depression.

The goals of this research are to investigate: (1) functional and neurochemical features associated with depression irrespective of clinical state; (2) moderating effects of hormones on stress circuitry in MDD; and (3) sex differences in symptoms. To this end, the study is enrolling adults with current depression and remitted depression, along with a control group of psychiatrically health adults. Participants will have an magnetic resonance imaging (MRI) exam involving multiple imaging techniques (functional, structural, spectroscopic) while performing computer-based tests. Additional questionnaires and tests will be done outside the scanner to assess current symptoms and hormone levels. The integration of laboratory-based measures of reward and stress sensitivity, with state-of-the-art imaging techniques and hormonal assessments promises to provide novel insights in the sex-dependent manifestation and pathophysiology of MDD.

Eligibility Criteria:
Inclusion Criteria for all participants.

* Males and females aged 18 through 25
* Capable of providing written informed consent, and fluent in English
* Right-handed
* Absence of any psychotropic medications for at least 2 weeks
* Female subjects will be scheduled to participate during the follicular phase of their menstrual cycle

Inclusion Criteria for "Current MDD" group:

* Meets inclusion criteria for all subjects, plus:
* Meets diagnostic criteria for a current episode of Major Depressive Disorder (MDD), as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

Inclusion Criteria for "Remitted MDD" group:

* Meets inclusion criteria for all subjects, plus:
* History of MDD as defined by DSM-5, but in remission for the past two months
* Absence of anxiety disorder for the past two months

Exclusion Criteria for all participants:

* History of psychiatric illnesses, other than depression or anxiety disorders among the Current MDD and Remitted MDD groups.
* History of psychotic episodes, suicidal ideation, or of electroconvulsive therapy (ECT) treatment
* Use of hormone replacement therapy, or of anabolic steroids.
* Use of hormonal contraceptives is permitted for female subjects only if the subject has regular menses
* Failure to meet any MRI safety requirements
* Serious or unstable medical illness, or history of neurological disease or damage
* History of use of cocaine, stimulants, or dopaminergic drugs
* History of substance use disorder or alcohol use disorder (as these terms are defined by DSM-5); except depressed subjects may have a history of 'Mild' substance/alcohol use disorder only if it ended as least 12 months ago.
Evaluation of COVA™+ CARD in Adult Cardiac Surgery

The aim of this observational study is to evaluate the safety of the guided healing and adhesion prevention membrane, COVA™+ CARD, in adult cardiac surgery. The causality of the collagen membrane according to the occurrence of peri and post-operative complications will be evaluated.

Assessment of the safety of COVA™+ CARD, collagen membrane to prevent adhesion appearance, in cardiac surgery in adult patients:

* collection of post-operative complications, causality of the membrane
* collection of complications in the 3-month period after the surgery, causality of the membrane
* collection of peri-operative complications, causality of the membrane
* collection of complications, 3 months after the surgery
* assessment of the efficacy of COVA™+ CARD if re-operation
* assessment of the surgeon's satisfaction

Eligibility Criteria:
Inclusion Criteria:

* 18 years of age or older
* Cardiac surgery using COVA™+ CARD

Exclusion Criteria:

* In accordance with the instruction for use (IFU) of the medical device.
* Refusal of participation to the study
Dietary Therapy In Epilepsy Treatment (DIET-Trial): A Randomised Non Inferiority Trial Comparing KD, MAD & LGIT for Drug Resistant Epilepsy

This randomised trial is undertaken to assess whether MAD or LGIT is non-inferior to KD with regard to seizure control at twenty-four weeks among children with drug resistant epilepsy. The hypothesis of the study is that in 1 to 15-year-old children with drug resistant epilepsy, use of Modified Atkins Diet (MAD) or Low Glycemic Index Therapy (LGIT) as an add on to the ongoing anti-epileptic drugs would not be inferior to ketogenic diet by \>15% in terms of seizure reduction from baseline seizure frequency at 24 weeks.

The primary outcome of the study is to determine the efficacy of MAD as compared to KD and LGIT as compared to KD for seizure reduction in drug resistant epilepsy following 24 weeks of dietary therapy in 1 to 15-year-old children on anti-epileptic drugs. The change in seizure frequency will be estimated as percentage change in seizure reduction at 24 weeks as compared to baseline.


Eligibility Criteria:
Inclusion Criteria:

1. Children aged 1-15 years with drug resistant epilepsy (Drug resistant epilepsy for the study will be defined as seizure frequency \>4 seizures per month, and treatment failure of ≥2 prescribed antiepileptic drugs).
2. Willing to come for regular follow up

Exclusion Criteria:

1. Surgically remediable cause for drug resistant epilepsy
2. Proven inborn error of metabolism except those in which KD is indicated (i.e., Pyruvate Carboxylase deficiency and GLUT-1 Deficiency)
3. Previously received KD, MAD or LGIT
4. Known case of

   1. Chronic kidney disease
   2. Chronic liver disease/ GI illness
   3. Chronic heart disease (congenital and acquired)
   4. Chronic respiratory illness
Effectiveness of Modafinil and D-amphetamine in Treating Cocaine Dependent Individuals

Cocaine dependence is a major public health problem; an effective primary treatment for cocaine dependent individuals has yet to be found. The purpose of this study is to examine the effects of d-amphetamine and modafinil, when given alone and in combination, in treating cocaine dependent individuals.

Cocaine is a strong central nervous system stimulant that is widely abused throughout the United Sates. Due to its widespread use, it is important to develop an effective treatment for cocaine dependence. Modafinil is a glutamate-enhancing agent. D-amphetamine is a central nervous system stimulant that is approved to treat individuals with narcolepsy and attention deficit disorder. Both modafinil and d-amphetamine may be effective treatments for cocaine dependence. The purpose of this study is to examine the effectiveness of modafinil and d-amphetamine, alone and in combination, in treating cocaine dependent individuals.

This study will last 16 weeks. Participants will be randomly assigned to one of four groups: 1) 60 mg dose of d-amphetamine; 2) 400 mg dose of modafinil; 3) 30 mg dose of d-amphetamine combined with 200 mg dose of modafinil; and 4) placebo. All participants will receive 200 mg of modafinil over 4 days.

Eligibility Criteria:
Inclusion Criteria:

* Meets Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV (SCID) criteria for cocaine abuse or dependence
* In general good health. Individuals who are HIV-positive will not be excluded if in good general health, unless medication interactions exist.

Exclusion Criteria:

* Meets diagnostic criteria for psychiatric disorders, including other forms of drug dependence, other than nicotine
* Current cardiovascular disease, as determined by an electrocardiogram
* On probation or parole if the circumstances do not allow study completion or if ethical constraints of supervision do not allow confidentiality
* Previously received treatment with d-amphetamine, modafinil, or aripiprazole
* Currently receiving prescribed medication
Foot Massage Applied Before a Bronchoscopy Procedure on Physiological Parameters and Anxiety

The goal of this randomized controlled trial is to assess the effectiveness of foot massage on physiological parameters and anxiety in patients undergoing bronchoscopy. The main questions it aims to answer are:

* Does foot massage applied before bronchoscopy affect physiological parameters?
* Does foot massage before bronchoscopy affect anxiety? Patients in the intervention group received foot massage once before bronchoscopy. Patients in the control group did not receive any treatment other than routine care.

After the ethics committee and institutional permissions were obtained, patients scheduled for bronchoscopy were evaluated by the researcher for eligibility. First of all, they were informed about the study. Those who agreed to participate and delivered written consent were included in the sample. Individuals were assigned to the intervention and control groups by using block randomization. To prevent interaction between groups, the data collection process of the control group was completed first.A Personal Information Form, the State-Trait Anxiety Inventory, and a Vital Signs Monitoring Form were used to collect study data. In the control group, data were collected during the first arrival of the individuals (T1), 40 minutes after T1 (T2), and following bronchoscopy (T3). No procedures were applied to the control group other than clinical protocols. After the data collection process of the study was completed, the questions of the patients in the control group were answered.

The data of the intervention group were collected during the first arrival of the individuals (before the massage) (T1), 40 minutes after T1 (after the massage) (T2), and following bronchoscopy (T3).

Massage sessions lasted approximately 40 minutes, including 20 minutes for each foot.

Eligibility Criteria:
Inclusion Criteria:

aged ≥18 years communicate verbally be conscious no lesions on the feet or any problems that may affect the feet (diabetes, neurological disorder, etc.), no previous history of bronchoscopy no history of problems or anxiety no history of any disorder no acute pain no use of opioids or strong sedatives in the last week before recruitment to the study

Exclusion Criteria:

patients who underwent emergency bronchoscopy patients who do not want to participate in the research voluntarily
Outcome of Patients Treated With RRT

Acute Kidney Injury (AKI) is a common serious complication after cardiac surgery. AKI not only prolongs the hospitalization time of patients undergoing cardiac surgery and increases the cost of treatment, but also is an independent risk factor for postoperative death. The aim of this study is to investigate the outcome of patients treated with renal replacement therapy (RRT), and to evaluate the short-term and long-term outcomes of patients with RRT.


Eligibility Criteria:
Inclusion Criteria:

* Critically ill patients undergoing cardiovascular surgery admitted to intensive care units.
* Patients receiving RRT for renal support
* Patients over 18 years of age

Exclusion Criteria:

* Patients \<18 years
* Refusal of consent