title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Hierarchical clustering and pathway analysis | Hierarchical clustering analysis was performed with MetaboAnalyst ( | PMC9825269 | ||
Validation | For proteomic analysis validation, fetuin-B measurements were performed using ELISA. Serum samples were diluted 1:10 000 with DPBS (Corning #20-031-CVR, Mediatech, Inc., Manassas, VA, USA) and kit-specific dilution buffer, and analyzed with a FETUB ELISA Kit (Cat No EKX-LDKNLJ-96; Nordic BioSite AB, Täby, Sweden), acco... | PMC9825269 | ||
Statistics | The distributions of protein changes were examined with the Shapiro–Wilk test. Most changes were skewed; thus, non-parametric tests were used for the analyses. The changes within the study groups were analyzed with the Wilcoxon test using the Benjamini–Hochberg procedure to control false discovery rates.To investigate ... | PMC9825269 | ||
Results | PMC9825269 | |||
Study subjects | high-density lipoprotein | The baseline characteristics of the participants are shown in Baseline characteristics of the study groups taking a 9-week course of combined oral contraceptive.EE, ethinylestradiol; DNG, dienogest; EV, estradiol valerate; WHR, waist–hip ratio; BP, blood pressure; HDL, high-density lipoprotein; LDL, low-density lipopro... | PMC9825269 | |
Proteomic analysis | PMC9825269 | |||
Protein identification | A total of 446 proteins or protein families with two or more unique peptides were quantified. Some of the protein sequences are shared by many proteins (protein families), and some are unique in the human proteome. Depending on which peptides are identified, one can detect either a distinct protein or a protein family.... | PMC9825269 | ||
Hierarchical clustering | Successful randomization was further confirmed by hierarchical clustering based on protein compositions (
| PMC9825269 | ||
Proteome alterations within groups | A total of 122 proteins/protein families changed significantly during the 9-week trial within at least one group: 121 in the EE + DNG and 5 in the EV + DNG group. No changes were observed in the DNG-only group. Some proteins were found in both low- and high-abundance fractions, indicating that proteins appeared both al... | PMC9825269 | ||
Change in protein abundances between study groups | The change in protein abundance from baseline to 9 weeks was significantly different between the study groups for 63 proteins/protein families. In all, 58 proteins/protein families altered differently between the EE + DNG and EV + DNG groups, 61 between EE + DNG and DNG only and 17 between EV + DNG and DNG only. All si... | PMC9825269 | ||
Pathway analysis | Most changes in the serum proteins were detected in the EE + DNG group; therefore, the functionality analysis was based on the proteins with a significant change during this treatment. The 10 most significantly affected pathways are listed in
Full lists of normalized abundance data are included in | PMC9825269 | ||
Fetuin-B, CBG and SHBG | After proteomic analysis, fetuin-B (a novel finding with a significant difference between the study groups) was chosen for additional validation. We previously reported the changes in CBG (
| PMC9825269 | ||
Discussion | non-alcoholic fatty liver disease | ACUTE PHASE RESPONSE, INFLAMMATION, LYSIS, NON-ALCOHOLIC FATTY LIVER DISEASE, INSULIN RESISTANCE, DYSLIPIDEMIA | This study showed that 9 weeks of EE-based COC use had a multifold effect on the serum proteome compared with EV-based COC or DNG-only preparation; the number of affected proteins after exposure to EE + DNG was 24-fold the number for EV + DNG and 120-fold that for DNG only. Few proteins changed during the use of EV + D... | PMC9825269 |
Supplementary Material | Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file. | PMC9825269 | ||
Acknowledgements | We thank M.Sc. Elisa Korhonen for statistical assistance and Mrs Maarit Haarala, Ms Elina Huikari and Mrs Pirjo Ikonen for expert technical assistance. | PMC9825269 | ||
Authors’ roles | T.T.P. | The study was designed by J.S.T. and O.H. in collaboration with T.T.P. and A.H. M.H.K., A.H., K.L., O.H., J.S.T. and T.T.P. contributed to the data collection. S.J., T.T., R.R., R.K.A. and M.H.K. performed the laboratory analyses and data interpretation. M.H.K. wrote the first draft of the manuscript; all authors contr... | PMC9825269 | |
Funding | Funding was obtained from Helsinki University Hospital research funds (J.S.T. and A.H.), the Hospital District of Helsinki and Uusimaa (K.L., T.T. and O.H.), the Sigrid Juselius Foundation (J.S.T. and T.T.P.), the Academy of Finland (J.S.T. and T.T.P. 315921 and 321763), the Finnish Medical Association (M.H.K., A.H. an... | PMC9825269 | ||
Conflict of interest | EVENTS | T.P. has received honoraria for lectures, consultations and research grants from Exeltis, Gedeon Richter, MSD, Merck, Pfizer, Roche, Stragen and Mithra Pharmaceuticals. O.H. occasionally serves on advisory boards for Bayer AG and Gedeon Richter and has designed and lectured at educational events for these companies. Th... | PMC9825269 | |
Data Availability | Normalized abundance data of high- and low-abundance fractions are included in | PMC9825269 | ||
References | PMC9825269 | |||
Introduction | Obesity, T2DM | OBESITY, TYPE 2 DIABETES | Obesity drives type 2 diabetes (T2DM) development. Laparoscopic adjustable gastric banding (LAGB) has lower weight reduction than other bariatric procedures. Liraglutide, a GLP-1 receptor agonist, improves weight and glycaemic control in patients with T2DM. This study aimed to determine the efficacy and safety of lirag... | PMC10599987 |
Methods | obesity, T2DM | OBESITY, SECONDARY | GLIDE, a pilot randomised, double-blind, placebo-controlled trial, evaluated LAGB with either liraglutide 1.8 mg or placebo in participants with T2DM and obesity. Participants were randomised (1:1) to 6-months therapy post-LAGB, with further 6 months off-treatment follow-up. The primary outcome was change in HbA1c from... | PMC10599987 |
Results | Twenty-seven participants were randomised to liraglutide ( | PMC10599987 | ||
Conclusions | SECONDARY | Our pilot data suggest no additional improvement in glycaemic control or BW with LAGB and liraglutide therapy. However, this trial was significantly underpowered to detect a significant change in the primary or secondary outcomes. Further trials are needed to investigate whether GLP-1 agonists, and particularly with mo... | PMC10599987 | |
Clinical trial registration | -11 | EudraCT number 2015-005402-11.
| PMC10599987 | |
Subject terms | PMC10599987 | |||
Introduction | Obesity, adiposity | OBESITY, ADIPOSITY | Obesity is defined as excess adiposity causing a deterioration in health [Bariatric surgical procedures include laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) [There is evidence underpinning adjunctive GLP-1 therapy post-bariatric surgery [ | PMC10599987 |
Methods | PMC10599987 | |||
Trial design and oversight | -11 | We conducted a randomised, double-blind, placebo-controlled trial at three sites in the United Kingdom. The study was prospectively registered with EudraCT (Registration Number: 2015-005402-11) and overseen by the sponsor, King’s Health Partners. The study was conducted in adherence with the Good Clinical Practice Guid... | PMC10599987 | |
Participants | We recruited adults (age 18–70) with a body mass index (BMI) of 30–50 kg/m | PMC10599987 | ||
Procedures | Participants underwent insertion of LAGB. Participants were randomised in a 1:1 ratio to either subcutaneous liraglutide 1.8 mg (Victoza) or placebo once daily within 6 weeks of surgery. Treatment allocation was fully concealed. Liraglutide was titrated as recommended to a maximum tolerated dose of 1.8 mg. The liraglut... | PMC10599987 | ||
Laparoscopic adjustable band procedures and follow up | CRF, ’ | CRF | This was a pragmatic trial. Although no specific surgical approach to LAGB placement was specified, as far as possible, standardisation in clinical approach was agreed upon amongst participating centres. The band’s type, size and specifications and operative procedure were documented in the clinical notes. When the gas... | PMC10599987 |
Randomisation | diabetes | DIABETES | Randomisation was carried out by the King’s Clinical Trials Unit through a web-based randomisation software utilising a minimisation algorithm. Minimisation, including a random component (0.8), was carried out to protect the balance between groups. Factors used in minimisation were centre, BMI (≤42 and >42), use of ins... | PMC10599987 |
Statistics | Diabetes, diabetes | REGRESSION, DIABETES, DIABETES | A statistical plan was drafted a priori and approved by the ethics committee. A sample size of 58 (29 per group) had 80% power to detect a 0.6% difference in HbA1c (above the minimum clinically important difference of 0.5%) between groups. This accounted for 20% drop-out or loss to follow-up. All analyses followed the ... | PMC10599987 |
Results | Between 27/03/2018 and 25/03/2020, 66 participants were screened for eligibility. Of these participants 39 were screen failures and 27 participants were randomly assigned to subcutaneous liraglutide 1.8 mg once daily or placebo for 6 months. Twenty-seven of the target 58 participants were therefore randomised to this t... | PMC10599987 | ||
Primary outcome: HbA1c | PMC10599987 | |||
HbA1c | At screening, median HbA1c was 51 mmol/mol in the liraglutide (L) arm and 58 mmol/mol in the placebo (P) arm (Difference in HbA1c and Body Weight at 6 months as well as at all other follow-up timepoints.Variables with missing data are indicated. All variables are reported as Median (Interquartile Range) due to a number... | PMC10599987 | ||
Body weight | At screening, the groups had an equivalent body weight of 107.4 kg (Table Supplementary Results Description | PMC10599987 | ||
Diabetes remission and glycaemic control | T2DM | On visual inspection of graphs depicting the distribution of T2DM duration between groups, (Supplementary Fig. | PMC10599987 | |
Concomitant medications | ® | At randomisation, on average, individuals in both arms were treated with one glucose-lowering agent. There were 14 recorded medications for the liraglutide arm; all patients were treated with metformin (13/13), and one was additionally treated with insulin (Tresiba®/degludec insulin). For the placebo arm, there were 20... | PMC10599987 | |
Adverse events | cholecystitis, gastro-intestinal symptom-related, vomiting | ADVERSE EVENTS, ADVERSE EVENT, CHOLECYSTITIS | Forty-two adverse events (AE) occurred during the trial: 32 were in the liraglutide arm, and 10 were in the placebo arm. There were three serious adverse events (SAEs) during the trial: 2 in the liraglutide arm and 1 in the placebo arm. The most serious occurred in the placebo arm: cholecystitis requiring cholecystecto... | PMC10599987 |
Band adjustments | Four participants (two in each treatment arm) had no reported band adjustments. On average participants had 3 band adjustments during the trial, this number did not significantly differ between groups (L:3.0, P:3.0, | PMC10599987 | ||
Discussion | cholecystitis, abdominal pain, gastrointestinal AEs, Weight loss, pain, weight gain, Diabetes, weight loss, T2DM, diabetes | CHOLECYSTITIS, ADVERSE EVENTS, SECONDARY, REMISSION, DIABETES, DIABETES | The GLIDE trial aimed to assess the metabolic impact of the addition of a GLP-1 receptor agonist in the form of liraglutide 1.8 mg once daily following a LAGB in patients with T2DM. We hypothesised that the addition of a GLP-1 receptor agonist would increase the efficacy of LAGB compared to LAGB alone. To our knowledge... | PMC10599987 |
Strengths and limitations | weight loss, T2DM | SECONDARY | The GLIDE clinical trial has several strengths. It used a randomised, double-blind, placebo-controlled design which increased the validity of the results. The study mirrors routine clinical care to reduce the patient burden taking part in the research. Finally the study provides data to power further randomised control... | PMC10599987 |
Conclusions | T2DM | SECONDARY | In conclusion, our pilot randomised controlled trial showed that the addition of the GLP-1 agonist receptor liraglutide after LABG did not significantly improve HbA1c or weight compared to placebo at 6 months. Importantly this trial was underpowered to detect a significant difference between groups in the primary and s... | PMC10599987 |
Supplementary information | The online version contains supplementary material available at 10.1038/s41366-023-01368-4. | PMC10599987 | ||
Acknowledgements | We thank the participants for taking part in the GLIDE trial. We would also like to thank the clinical research teams at each study site who worked on the GLIDE trial. This study was funded by Novo Nordisk Investigator Led Grant. Novo-Nordisk had no input in the design, conduct, or interpretation of the results. | PMC10599987 | ||
Author contributions | All authors made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted. BM tak... | PMC10599987 | ||
Data availability | Data for the trial are available upon reasonable request to the corresponding author. | PMC10599987 | ||
Competing interests | Johnson & Johnson, Boehringer | AEL does not declare any conflicts of interest. CLR declares grants to his institution from the Irish Research Council, Health Research Board, Science Foundation Ireland and Anabio; consulting fees from NovoNordisk, Eli Lily, Johnson & Johnson, Boehringer Ingelheim, GI dynamics and Herbalife; Honoraria for presentation... | PMC10599987 | |
Ethics approval | Approved by London – Westminster Research Ethics Committee (REC Reference: 16/LO/1144). | PMC10599987 | ||
References | PMC10599987 | |||
Objectives | Augmented reality (AR), which entails overlay of in situ images onto the anatomy, may be a promising technique for assisting image-guided interventions. The purpose of this study was to investigate and compare the learning experience and performance of untrained operators in puncture of soft tissue lesions, when using ... | PMC10017581 | ||
Methods | Forty-four medical students (28 women, 16 men) who had completed a basic US course, but had no experience with AR US, were asked to perform US-guided biopsies with both sUS and AR US, with a randomized selection of the initial modality. The experimental setup aimed to simulate biopsies of superficial soft tissue lesion... | PMC10017581 | ||
Results | Despite having no experience with the AR technique, time to puncture did not differ significantly between AR US and sUS (median [range]: 17.0 s [6–60] and 14.5 s [5–41], | PMC10017581 | ||
Conclusions | Students considered AR US to be the preferable and more enjoyable modality for learning how to obtain soft tissue biopsies; however, they did not perform the biopsies faster than when using sUS. | PMC10017581 | ||
Key Points | • • • | PMC10017581 | ||
Keywords | Open access funding provided by University of Zurich | PMC10017581 | ||
Introduction | HMD | Within the last few years, virtual reality and augmented reality (AR) have been increasingly used in the fields of entertainment and gaming. More recently, they have also been implemented in the field of medicine, particularly for training [For example, superimposing a computed tomography (CT) image over anatomical str... | PMC10017581 | |
Materials and methods | PMC10017581 | |||
Operators | The institutional review board approved this prospective, randomized study, and the participants gave their consent to participation.The study cohort comprised 44 medical students (28 women, 16 men) who had no experience in performing biopsies but had completed a standard US course (16 lessons). | PMC10017581 | ||
Soft tissue/breast phantom (as used by the Minimally Invasive Breast Biopsies Working Group of the Swiss Society of Radiology) | The breast phantoms comprised four turkey breasts (each 2–3 kg) filled with olives (Ultrasound guided biopsy using standard US (sUS). Note the turkey breast containing olives simulating a breast with soft tissue lesions | PMC10017581 | ||
US techniques | The sUS system used was a GE Logiq S7 expert (General Electric) with a matrix linear probe (ML 6-15) (Fig. The AR in situ US was composed of a conventional US system (SuperSonic Aixplorer Ultimate) with a linear probe (SL 18-5) and custom-developed software that transmitted the US image to an industry-grade head-mounte... | PMC10017581 | ||
Briefing of the operators before the procedure performance | Before the experiments, students were instructed during 15 min in a standardized fashion regarding the usage of the probe, locating and targeting the lesion, as well as performing the biopsy. | PMC10017581 | ||
Study workflow | FEMALE BREAST, SECONDARY | Each participant was required to puncture the turkey breast containing the olive-simulated lesions with a 14G disposable core biopsy needle (Bard Magnum) used in concert with a Bard Magnum Biopsy instrument. The students were asked to perform the procedure three times using AR in situ US and three times using sUS. The ... | PMC10017581 | |
Statistical analysis | Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 27. Descriptive statistics were used to express career aspiration by gender, self-assessment of manual skills, history of playing video games, significant coordinative skills, and number of missed hits using sUS and AR US. Further descri... | PMC10017581 | ||
Discussion | HMD | MINOR, INFILTRATION | Use of AR technology is increasing in several fields, including medicine. Early adaptations include image-guided infiltrations [We failed to confirm that our initial hypothesis, which was that inexperienced operators would perform biopsies of soft tissue lesions faster when using AR US than when using sUS, as demonstra... | PMC10017581 |
Acknowledgements | We would like to thank Connie Maag, medical practice assistant, and Silke Callies, study nurse, both at the Institute of Radiology, Kantonsspital Baden, Mirdita Useini, and Yaël Weissmann from the medical education team at ETH Zurich, as well as Regula Schüppbach, study nurse, at the Balgrist University Hospital, for t... | PMC10017581 | ||
Funding | Open access funding provided by University of Zurich. The study has been supported by an unrestricted grant of Bayer (Schweiz) AG. | PMC10017581 | ||
Declarations | PMC10017581 | |||
Guarantor | The scientific guarantor of this publication is Nadja A. Farshad-Amacker. | PMC10017581 | ||
Conflict of interest | The authors of this manuscript declare relationships with the following companies: Incremed, Zurich, Switzerland. The husband of NF is cofounder and shareholder of the company Incremed (start-up company of the University of Zurich), who invented the augmented reality system (including patent) | PMC10017581 | ||
Statistics and biometry | Two of the authors have significant statistical expertise (ChK and JG). | PMC10017581 | ||
Informed consent | No informed consent was needed in this phantom study. | PMC10017581 | ||
Ethical approval | Institutional Review Board approval was obtained. | PMC10017581 | ||
Methodology | • prospective• experimental study• multicenter study | PMC10017581 | ||
References | PMC10017581 | |||
Background | PCOS, endocrine disorder | POLYCYSTIC OVARY SYNDROME 1, ENDOCRINE DISORDER | Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder with a variety of symptoms. Current treatment options include the contraceptive pill as well as metformin, however both treatments are limited to specific symptoms and have common side effects. | PMC10106320 |
Methods | PCOS | SECONDARY | This phase IV study is a monocentric, double blinded randomized clinical trial comparing the effects of six months of probiotic intervention to a placebo, with an additional open-label metformin arm as a positive control in a total of 180 participants with PCOS. The first of three visits is the screening visit, where i... | PMC10106320 |
Discussion | PCOS | Based on new insights into the role of the gut microbiome in PCOS development, this study is exploring the potential of using probiotics to treat women with PCOS symptoms. If successful, this new therapy approach could open a new realm of possibilities for treating PCOS. To our knowledge, this is the first study compar... | PMC10106320 | |
Registration | -20 | EudraCT number: 2020-000228-20. Clinicaltrials.gov identifier: NCT04593459. | PMC10106320 | |
Protocol version | Version 1.5 dated 29th November 2021. | PMC10106320 | ||
Keywords | PMC10106320 | |||
Background | PMC10106320 | |||
PCOS and current therapeutic options | obesity, metabolic disorder, PCOS, hirsutism, weight loss | OBESITY, METABOLIC DISORDER, INSULIN RESISTANCE, HIRSUTISM, POLYCYSTIC OVARY SYNDROME 1 | Polycystic Ovary Syndrome (PCOS) is a hormonal and metabolic disorder affecting up to 20% of women worldwide, depending on the diagnostic criteria used [As the exact pathomechanisms of PCOS have not yet been established, therapeutic options mainly focus on specific symptoms. For obesity, insulin resistance and other me... | PMC10106320 |
PCOS and microbiome interactions | PCOS | Our group was among the first to discover lower bacterial abundances and significant differences in stool microbiome composition between women with PCOS and healthy controls in 2017 [Gut microbiota also play a critical role in phytoestrogen metabolism in our body. For women with PCOS, the isoflavone metabolite equol ma... | PMC10106320 | |
Hypothesis and objectives | PCOS, PCOS symptoms | SECONDARY | The working hypothesis of this randomized controlled trial (RCT) is an improvement of PCOS symptoms and androgen levels after six months of probiotic intervention. To that end, the trial is designed to primarily compare the probiotic intervention to a placebo treatment and secondarily to a standard non-hormonal treatme... | PMC10106320 |
Methods and analysis | PMC10106320 | |||
Study design | This phase IV trial is monocentric, randomized and double-blinded with one additional open-label treatment arm serving as the positive control. Two randomizations are performed. In the first randomization, participants are randomized in a 2:1 ratio to either the double-blind part or open-label metformin part. This open... | PMC10106320 | ||
Timeline | depression, PCOS | For this purpose, potential participants have a screening visit, where participants give written informed consent, blood and urine samples are collected and extensive patient history as well as questionnaires on PCOS symptoms, probiotic intake, depression symptoms and diet are collected. A soy challenge test as well as... | PMC10106320 | |
Eligibility criteria | cancer, PCOS, gastrointestinal tract, allergies, stoma, acute gastrointestinal infection, hyperandrogenism, chronic disease | INFLAMMATORY BOWEL DISEASE, CANCER, TYPE 1 DIABETES, MALIGNANCIES, ALLERGIES, HYPERANDROGENISM, TYPE 2 DIABETES, CHRONIC DISEASE | In order to be eligible for the trial, women should be between 18 and 45 years of age, they should have at least two out of three Rotterdam criteria and they have to sign the informed consent form before starting the trial.Women can only participate if they do not have: hyperandrogenism of any cause other than PCOS; pr... | PMC10106320 |
Intervention | PMC10106320 | |||
Probiotic and placebo | ® | The main intervention in this trial is a dietary food supplement powder containing seven probiotic bacterial strains: lactobacillus salivarius W57, lactobacillus casei W56, lactobacillus rhamnosus W71, lactococcus lactis W58, enterococcus faecium W54, lactobacillus plantarum W62 and lactobacillus acidophilus W22 (manuf... | PMC10106320 | |
Metformin | The metformin drug used in this trial is Glucophage, a commercially available extended release metformin-hydrochloride pill, owned by Merck GmbH, Vienna, Austria. It is packaged in boxes containing 200 pills with no special markings regarding the trial. | PMC10106320 | ||
Blinding | COMPLICATIONS | The blinding is applied to the trial participants and the investigators, who serve as both care providers and outcome assessors.A treatment code table was generated via Winclove Probiotics B.V., Netherlands. Each Verum/Placebo box containing 50 sachets receives a unique code, corresponding to the treatment code table. ... | PMC10106320 | |
Concomitant therapies | infection, PCOS, CRF | INFECTION, THYROID, CRF | Apart from the metformin and the probiotic formula as well as the placebo, no additional medicinal products will be administered by the investigators as part of this study. However, a subgroup of PCOS patients has additional diagnoses and therefore we need to account for any medications the participants might have to t... | PMC10106320 |
Outcome parameters | PMC10106320 | |||
Primary outcome | PCOS | The primary endpoint of the study is a change in serum free testosterone concentration in women with PCOS after a 6-month intervention with probiotics compared to placebo treatment.PCOS combines several different phenotypes and symptoms which may vary greatly, however free testosterone is one of the most consistent bio... | PMC10106320 | |
Secondary outcomes | inflammation, depression, PCOS | INFLAMMATION |
Glucose metabolism via HOMA and Matsuda indices as determined through an oral glucose tolerance test.Other hormonal parameters of PCOS (Anti-Müllerian hormone; androstenedione; follicle-stimulating hormone FSH; luteinizing hormone LH; dehydroepiandrosterone-sulphate DHEA-S; 17α-hydroxy-progesterone; 17β-hydroxy-estrad... | PMC10106320 |
Exploratory outcome measures |
Lipid metabolism (low-density lipoprotein LDL; high-density lipoprotein HDL; lipoprotein a LP(a); triacylglycerol;)FACS analysis (B cell subtypes).Metabolomics of stool and blood.Gene expression analysis in blood and biopsy samples.Changes in incretin levels. | PMC10106320 |
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