cyrilzakka/clinical-trials huggingface dataset:
How Secreted-embryo-derived Trypsin Initiates, Maintains and Terminates Ca2+ Signals in Uterine Epithelial Cells

To develop a deeper understanding of endometrial-embryo crosstalk through basic research, uncover therapeutic targets and to improve reproductive outcome.

Pregnancy is a complex and highly coordinated physiological process that involves implantation of a hatched blastocyst into a decidualizing endometrium. The main purpose of implantation is to ensure that the blastocyst firmly anchors into the decidual stroma, which allows further development by enabling placentation. Although a multitude of cellular events and molecular pathways involved in embryo-uterine crosstalk have been identified in mouse models, a comprehensive understanding of human embryo-uterine interaction is still missing. Our work indicates that endometrial epithelial Ca2+ signalling in response to serine proteases released by human embryos plays an important role in maternal recognition and selection of the conceptus at implantation. Previous studies have demonstrated that trophoblast spheroids can elevate \[Ca2+\]i in human uterine epithelial cell line (Ishikawa) by activating Ca2+ entry via mechano-sensitive Ca2+ permeable channels leading to the induction of epithelial adhesiveness. However, the mechanism(s) mediating the protease-induced \[Ca2+\]i transients in human uterine epithelium have not been studied to date. Investigators hypothesise that Na+ entry into the intravillous space via trypsin-activated ENaC will depolarise the cellular membrane and increase \[Na+\]v sufficiently high to reverse the sodium/calcium exchanger providing means for Ca2+ entry into the intravillous space. Ca2+ diffusion from the microvilli into the bulk cytoplasm will increase \[Ca2+\]i and, in parallel with SOCE, act as a source for re-filling of the ER. Increased \[Ca2+\]i will also activate the BK channels leading to repolarisation and termination of Ca2+ entry via the NCX.

By using spent medium from embryos, which will undergo pre-implantation genetic testing, it will become possible to determine, whether the above mentioned mechanisms are influenced by the ploidy status of the embryo.

Eligibility Criteria:
Inclusion Criteria:

* Couples with primary / secondary infertility who are planned to undergo ICSI treatment with PGT-A
* Age of each partner above 18 years

Exclusion Criteria:

* Couples with consanguinity (couple who is 1st or 2nd degree cousins)
* Couples in whom the female partner has a history of:
* Chemotherapy or radiation which impacts the ovarian reserve
* Surgery at the ovaries / adnex region
* Endometriosis
* Couples in whom the male partner has a history of:
* Chemotherapy / Radiation which impacts the semen result
* Surgery at the testicles
* Vasectomy
* Surgery for reversal of vasectomy
* Semen obtained by fine needle aspiration (FNA) or Testicular sperm extraction (TESE)
The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity

Hypoglycaemia unawareness is a common complication in patients with type 1 diabetes and with insulin-treated type 2 diabetes of long duration. The loss of autonomic symptoms to hypoglycemia does not solely depend on loss of adrenaline responses.Differences in sensitivity to catecholamines may also be involved.

Reconciling the data on β2-adrenergic receptor polymorphism to those on loss of β-adrenergic sensitivity in diabetic patients with hypoglycemia unawareness, we hypothesize that hypoglycemia unawareness is at least partly the result of desensitization of the β2-adrenergic receptor and that patients who are homozygous for arginine at codon 16 are particularly susceptible for this desensitization process, whereas patients who are homozygous for glycine at codon 16 are resistant for desensitization.

Objectives

1. To determine whether, and if so to what extent, antecedent hypoglycemia reduces β2-adrenergic sensitivity in healthy subjects with Arg16 homozygosity.
2. To investigate whether or not healthy subjects with Gly16 homozygosity are resistant to desensitization
3. To confirm that antecedent hypoglycemia reduces the heart rate response to isoproterenol and to assess to what extent this reduced response is mediated by impairments in baroreflex sensitivity.


Eligibility Criteria:
Inclusion Criteria:

* Informed consent
* Homozygous for Arginine at codon 16 or homozygous Gly at codon 16
* No regular usage of medication other than oral contraceptives

Exclusion Criteria:

* History of cerebrovascular, cardiovascular, or peripheral vascular disease
* Smoking
* Alcohol usage of more than 10 units per week
* Inability to abstain from xanthine-derivatives (coffee, tea, cola, chocolate, cacao) or alcohol for 2 days
* BMI above 30 kg/m2
* Participation to any other trial in the preceding 3 months
* Ongoing disease of any kind
* Pregnancy
TnThs Predicting Evolving Non-STEMI

BACKGROUND: We sought to determine the diagnostic value of the new TnThs assay for early detection of evolving non-STEMI in patients with acute coronary syndrome and a negative 4th generation cTnT result on admission.

METHODS: We evaluated several statistical patterns of blood results of TnT hs and cTnT of 115 patients and calculated necessity of prediction of evolving non-STEMI within 6 hours.

RESULTS: Based on the results of the 4th generation cTnT assay, an evolving non-STEMI was diagnosed in 26 patients, 31 were classified as unstable angina. The TnThs lead to an increase of non-STEMI diagnosis as compared to the 4th generation assay. We could calculate increased sensitivities for earlier detection of evolving non-STEMI from 61.5% on admission to 90.9% within 3 hours and 100% within 6 hours compared to cTnT.

CONCLUSIONS: The TnThs assay enables earlier detection of non-STEMI and allows identification of an additional percentage of cases with non-STEMI previously classified as unstable angina.


Eligibility Criteria:
Inclusion Criteria:

* 115 consecutive patients were enrolled with symptoms suggestive of ACS, admitted to the Chest Pain Unit of the University of Heidelberg. All patients received a 12-lead electrocardiogram (ECG) recording on admission, and a second 12-lead ECG after 6 hours

Exclusion Criteria:

* Patients who underwent percutaneous coronary intervention (PCI) during follow-up sampling were excluded as were patients with a significant kidney dysfunction defined as an estimated glomerular filtration rate below 60 ml/min/1.73m2.
* Patients with STEMI were excluded.
* Patients with only 1 blood sample were also excluded.
Additive Effect of Twice-daily Brinzolamide 1%/Brimonidine 0.2%Combination as an Adjunctive Therapy to Travoprost in Patients With Normal Tension Glaucoma

The purpose of this study was to determine the incremental intraocular pressure (IOP) lowering that is achieved when Simbrinza is used adjunctively to Travatan in patients with normal tension glaucoma that may benefit from further IOP lowering.

This study was prematurely terminated due to administrative reasons and not due to any safety or efficacy concerns.

Eligibility Criteria:
Inclusion Criteria:

* Sign written informed consent
* Diagnosed with normal tension glaucoma
* Intraocular pressure measurements in at least 1 eye as specified in the protocol
* Willing and able to attend all study visits

Exclusion Criteria:

* History of hypersensitivity to any of the study drugs
* Use of medications prohibited by the protocol
* Pregnant or nursing
* Of child-bearing potential unless using contraception, as specified in the protocol
* Any form of glaucoma other than open angle glaucoma in either eye
* Chronic, recurrent or severe inflammatory eye disease
* Ocular trauma or surgery within the past 6 months in either eye; ocular infection or laser surgery within the past 3 months in either eye (all from screening)
* Conditions which would make the patient, in the opinion of the Investigator, unsuitable for the study.
Scapholunate Ligament Reconstruction: Early Dart Throwing Motion Versus Motion in Anatomical Planes

Patients undergoing scapholunate ligament reconstruction at Balgrist University Hospital are divided into two groups and receive two different types of mobilisation postoperatively. The investigators will compare the outcome (pain, strength, mobility) between the two groups 1 year after the operation.

The so-called 'dart-throwing motion' (DTM) plane of movement, from radial extension to ulnar flexion, has gained attention as it has been shown to be an important axis of wrist movement during activities of daily living. Further studies have shown that during movement of the intact wrist in the dart throwing plane, most of the movement occurs in the mediocarpal joint, while the proximal row remains relatively immobile.

In scapholunate (SL) ligament reconstruction using the flexor carpi radialis tendon, the SL interval is immobilised using 2 Kirschner wires for 8-10 weeks to relieve the strain on the ligament and allow it to heal. From the 2nd postoperative week, mobilisation is started using DTM mobilisation or mobilisation in the anatomical plane. The aim of the study is to investigate in a randomised trial whether mobilisation in the anatomical plane produces the same postoperative results.

In this project, the investigators will compare two types of mobilisation in the rehabilitation of SL ligament reconstruction. The participants will be randomised to two treatment groups. This procedure therefore corresponds to a risk category A in 'other' clinical trials according to Chapter 4 ClinO.

Eligibility Criteria:
Inclusion Criteria:

* SL Ligament reconstruction at Balgrist University Hospital
* at least 18 years
* Written informed consent

Exclusion Criteria:

* Age under 18 years
* Refusal of participation
* Pregnancy
Characterizing Myositis With 68Ga-FAPI PET/CT

To evaluate the potential usefulness of 68Ga-FAPI PET/CT for the diagnosis and evaluation of systemic involvement in idiopathic inflammatory myopathies (IIM)/myositis, and compared the results with those of 18F-FDG PET/CT.

Inflammatory myopathies (IIM), collectively known as myositis, are heterogeneous systemic autoimmune disorders characterized by muscle inflammation, and frequently accompanied by extra-muscular manifestations that affect the skin, lung, and joints. Prevalence of underlying malignancy is high in patients with IIM.

68Ga-FAPI has been developed as tracers specific for fibroblast-activation protein (FAP), which is overexpressed in activated fibroblasts in various type of cancers and autoimmune diseases, such as rheumatoid arthritis, IgG4-related diseases and interstitial lung diseases.

Recently the investigators have published articles of the application of 68Ga-FAPI in IgG4-related disease and rheumatoid arthritis, which showed it was more sensitive than FDG in detecting a certain type of inflammation, and the potential utility of FAP-targeted PET/CT imaging for disease assessment in myositis have been reported in a case recently.

Thus, this prospective study is going to investigate utility of 68Ga-FAPI PET/CT in diagnosis, disease assessment including skeletal muscle involvement, cardiac involvement, interstitial lung diseases and potential underlying cancer screening, response to treatment and prognosis, compared with 18F-FDG PET/CT.

Eligibility Criteria:
Inclusion Criteria:

1. A diagnosis of myositis according to American College of Rheumatology/European League Against Rheumatism 2017 (ACR/EULAR 2017) criteria
2. Adult men or women 18 and ≤ 75 years of age at the time of signing the informed consent (ICF).
3. Participants who were able to provide informed consent (signed by participant or legal representative) and assent according to the guidelines of the Clinical Research Ethics Committee.
4. 68Ga-FAPI and 18F-FDG PET/CT were performed within two weeks.

Exclusion Criteria:

1. Pregnancy;
2. Breastfeeding;
3. known allergy against FAPI;
4. any medical condition that in the opinion of the investigator may significantly interfere with study compliance.
Optimal Management of Malignant Dysphagia

According to the Canadian Cancer Society there are approximately 1700 new cases of esophageal cancer per year in Canada. As most of these patients are diagnosed in advanced stages of the disease, 1800 deaths are estimated from this cancer annually . Progressive dysphagia is the most common presenting symptom and impacts not only the patient's quality of life but the ability to tolerate life prolonging treatments such as systemic chemotherapy.

Although there are several therapeutic modalities to alleviate malignant dysphagia including laser, photodynamic therapy and cryotherapy , the use of stents and radiotherapy are the most commonly employed. However, the optimal approach to effective, timely treatment of malignant dysphagia remains a challenge. The investigators conducted a preliminary retrospective review to investigate such palliation procedures and found that a multi-modality approach may yield the most favourable results .

Therefore, our clinical trial will examine the effectiveness of adding a single dose of brachytherapy to patients with severe dysphagia who have already been treated with a endoscopically placed self-expanding metallic stent.


Eligibility Criteria:
Inclusion Criteria:

* Age ≥18 years
* Confirmed esophageal/gastroesophageal (GEJ) cancer (Siewert Type I and Type II only) of any histology on biopsy
* Dysphagia score ≥2
* Stage IV cancer/Metastatic disease

Exclusion Criteria:

* Expected life expectancy \< 3 months
* Inability to undergo stent insertion
* Siewert Type III gastroesophageal cancer
* Esophageal-Airway fistula
A Phase 1b Study of SGN-75 in Combination With Everolimus in Patients With Renal Cell Carcinoma

This is a phase 1, open-label, dose-escalation clinical trial to evaluate the safety of SGN-75 in combination with everolimus in patients with CD70-positive metastatic renal cell carcinoma.


Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of metastatic renal cell carcinoma with confirmed CD70 expression
* Previously treated with at least 1 tyrosine kinase inhibitor (TKI)
* Measurable disease
* Eastern Cooperative Oncology Group performance status 0 or 1
* Adequate lung and renal function

Exclusion Criteria:

* Prior treatment with anti-CD70-directed therapy
* Received more than one prior treatment with an mTOR inhibitor
Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer

Recent clinical studies have demonstrated a reduction of irinotecan (CPT-11) gastrointestinal toxicities when the CPT-11 is administered in combination with thalidomide in patients with diagnosis of gastric cancer. The main purpose of this study is to investigate the efficacy and safety of thalidomide and CPT-11 in advanced gastric cancer. The investigators will also manage to find out the possible interactions between CPT-11 pharmacokinetics and thalidomide to explain the previously described gastrointestinal toxicity reduction.

This is a prospective, randomized, multi-center, controlled clinical trial, aimed to evaluate efficacy and tolerability of thalidomide and CPT-11 in advanced gastric cancer. A total of 900 patients are planned to be enrolled into the study. Patients with diagnosis of advanced gastric cancer will be randomized into two groups, and be treated with thalidomide+ CPT-11 or CPT-11, respectively. The primary end point is time to progression (TTP), and the secondary end points include efficacy, overall survival (OS) and the occurrence of delayed diarrhea.

Eligibility Criteria:
Inclusion Criteria:

* 18y \<Age\<75y
* Patients with histologically proven tumor focus will be eligible for this protocol
* Measurable or assessable disease
* At least 4 weeks since last chemotherapy ;chemotherapy regimens without Irinotecan
* No hepatic, renal and hematopoietic dysfunction; no hemorrhage of digestive tract,obstructive jaundice, gastrointestinal perforation or obstruction
* ECOG PS:0-2
* Expected OS ≥ 3 months

Exclusion Criteria:

* obstruction of digestive tract, thrombosis or other intolerant side effects during treatment
Rapidity of Response to Adalimumab Treatment in Patients With Crohn´s Disease

The purpose of this study is to evaluate the rapidity of onset of clinical response to adalimumab therapy in patients with luminal Crohn's disease.


Eligibility Criteria:
Inclusion Criteria:

* Crohn's disease (CD) diagnosed within, at least, the previous 4 months.
* Patients with active luminal (Harvey-Bradshaw Index \[HBI\] ≥ 8) moderate to- severe CD.
* No response to a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant.
* If receiving any of the following treatments, their dose should be stable during the periods indicated:

  * Aminosalicylates for, at least, the last 4 weeks
  * Probiotics for, at least, the last 4 weeks
  * Analgesics for, at least, the last 4 weeks
  * Antidiarrheals for, at least, the last 4 weeks
  * CD-related antibiotics for, at least, the last 4 weeks
  * Azathioprine, 6-mercaptopurine or methotrexate for, at least, the last 12 weeks
* If receiving any of the following treatments, their dose should not have been increase in the past two weeks (the dose reduction is permitted):

  * Oral budesonide (maximum dose of 9 mg/day)
  * Oral prednisone or equivalent (maximum dose of 40mg/day)

Exclusion Criteria:

* Previous treatment with any anti-Tumor Necrosis Factor agent
* Surgical bowel resection within the previous 6 months, ostomy, extensive bowel resection (\> 100 cm), short bowel syndrome
* Fistulising Crohn's disease
* Treatment with cyclosporine or tacrolimus within the previous 8 weeks
* Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from screening, congestive heart failure of worse than grade II New York criteria (New York Heart Association Functional Classification).
* Subject with an ostomy or ileoanal pouch, proctocolectomy, total colectomy, ileostomy, stoma or ileal pouch-anal anastomosis (Subjects with a previous ileo-rectal anastomosis are not excluded).
* Screening laboratory values (according to central laboratory)
* Known hepatitis C (HC) infection.
* Serologic evidence of hepatitis B (HB) infection based on the results of testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs) antibodies.
VestibulOTherapy: Vestibular Impact on Learning

Research Question: Will daily engagement in activities tailored to the evidence-based vestibular research result in improved attention and learning outcomes for children ages 6-9 years of age after an 8-week classroom-based intervention?

"Vestibulotherapy" is an emerging frame of reference aiming to help neurotypical children with under-performing vestibular systems develop neural pathways supporting communication and learning.

Theory based upon systematic review: Given adequate vestibular activation through targeted activities (in an otherwise under-performing vestibular system), myelination and neuroplasticity propagate along learning pathways leading to greater neural connectivity and efficiency for sequencing, ordinance, attention, memory, body schema, spatial cognition, executive function, and interoception.

As a result of prescribed vestibular interventions and gained attributes supporting learning, students will experience increased academic growth and success as outlined by the following model.

Eligibility Criteria:
Inclusion Criteria:

* neurotypical development
* between the ages of 6-10 years of age
* performance challenges in school in the areas of math, spelling, organization, sequencing, attention, or engagement
* demonstrate attributes of vestibular dysfunction per the Vestibular Profile
* may have ADD or ADHD
* May have challenges with speech articulation
* good potential for learning and engaging in prescribed interventions

Exclusion Criteria:

* Neurodiverse development (with the exception of ADHD or ADD)
* Absence of vestibular challenges
* Absence of learning challenges.
* unable to participate in interventions on a routine basis due to attendance or other limitations.
Evaluating an Under-mattress Sleep Monitor Compared to a Peripheral Arterial Tonometry Device in the Diagnosis of Obstructive Sleep Apnea

A device has been developed which is placed under the mattress, thereby escaping contact with patient, which enables monitoring of sleep activity and has been shown in some studies to provide an estimate of the frequency of sleep disordered breathing. If the estimates of sleep disordered breathing from this new device are medically equivalent to current excepted home sleep apnea test devices within clinically important ranges of sleep disordered breathing, it may have several benefits. This study is designed to help answer several important clinical questions, namely, is the new device clinically equivalent to an established HSAT device for patients who have at least moderately severe OSA, and what is the effect of multiple nights on classification of severity and presence of OSA.

The design will be a prospective test of two diagnostic testing strategies. The tests will take place in the same patient concurrently, so the patient's results from one test will serve as the comparator with the other test device. No randomization or blinding is needed.

Patients will be recruited from the Mayo Clinic Center for Sleep Medicine (and another sleep center with enriched racial variety). Consecutive patients in whom the clinician has ordered a WatchPAT™ will be potential candidates for an opportunity to participate in the study. Patients will be made aware of the trial by invitation from members of the healthcare team. Interested patients will be evaluated according to the inclusion and exclusion criteria.

Eligibility Criteria:
Inclusion Criteria:

Clinician suspects of having OSA due to presence of any:

* STOP-BANG ≥ 3,
* overnight oximetry with ODI ≥ 5,
* STOP-BANG≥ 2 and one or more of: disrupted sleep, cognitive complaints, paroxysmal or prior atrial-fibrillation (now in NSR), stroke, TIA
* Has a smartphone capable of running both Withings and Itamar's app
* Stable sleeping quarters and schedule (i.e., no overnight shifts) for at least 7 days
* Domicile has capable wireless internet service

Exclusion Criteria:

* Uses short-acting nitrates within 3 hours of the study
* Has a permanent pacemaker
* Atrial fibrillation or sustained supraventricular arrhythmias
* Known congestive heart failure Class ≥ 1, or known LVEF\< 45%
* Sustained hypoxemia or hypoventilation (results of RA daytime ABG show SaO2\<90% or PaCO2\>45 mmHg, or overnight oximetry shows mean SaO2\<90%.)
* Advanced pulmonary disease (COPD GOLD stage ≥ II , pulmonary fibrosis with GAP ≥ 1 or significant dyspnea on exertion