bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range
Authors: Eide Kvitne Kine , Hole Kristine , Krogstad Veronica , Wollmann Birgit Malene , Wegler Christine , Johnson Line K. , Hertel Jens K. , Artursson Per , Karlsson Cecilia , Andersson Shalini , Andersson Tommy B. , Sandbu Rune , Hjelmesæth Jøran , Skovlund Eva , Christensen Hege , Jansson-Löfmark Rasmus , Åsberg Anders , Molden Espen , Robertsen Ida 
Published: June 2022

AbstractPurposeVariability in cytochrome P450 3A4 (CYP3A4) metabolism is mainly caused by non-genetic factors, hence providing a need for accurate phenotype biomarkers. Although 4β-hydroxycholesterol (4βOHC) is a promising endogenous CYP3A4 biomarker, additional investigations are required to evaluate its ability to predict CYP3A4 activity. This study investigated the correlations between 4βOHC concentrations and hepatic and intestinal CYP3A4 protein expression and ex vivo microsomal activity in paired liver and jejunum samples, as well as in vivo CYP3A4 phenotyping (midazolam) in patients with a wide body weight range.MethodsThe patients (n = 96; 78 with obesity and 18 normal or overweight individuals) were included from the COCKTAIL-study (NCT02386917). Plasma samples for analysis of 4βOHC and midazolam concentrations, and liver (n = 56) and jejunal (n = 38) biopsies were obtained. The biopsies for determination of CYP3A4 protein concentration and microsomal activity were obtained during gastric bypass or cholecystectomy. In vivo CYP3A4 phenotyping was performed using semi-simultaneous oral (1.5 mg) and intravenous (1.0 mg) midazolam.Results4βOHC concentrations were positively correlated with hepatic microsomal CYP3A4 activity (ρ = 0.53,p < 0.001), and hepatic CYP3A4 concentrations (ρ = 0.30,p = 0.027), but not with intestinal CYP3A4 concentrations (ρ = 0.18,p = 0.28) or intestinal microsomal CYP3A4 activity (ρ = 0.15,p = 0.53). 4βOHC concentrations correlated weakly with midazolam absolute bioavailability (ρ =  − 0.23,p = 0.027) and apparent oral clearance (ρ = 0.28,p = 0.008), but not with systemic clearance (ρ =  − 0.03,p = 0.81).ConclusionThese findings suggest that 4βOHC concentrations reflect hepatic, but not intestinal, CYP3A4 activity. Further studies should investigate the potential value of 4βOHC as an endogenous biomarker for individual dose requirements of intravenously administered CYP3A4 substrate drugs.Trial registrationClinical.Trials.gov identifier: NCT02386917.
Detection of reproductive trade-offs is influenced by resource availability and maintenance: an experimental study in the burying beetle (Nicrophorus vespilloides)
Authors: Wang Wenxia , Ma Long , Versteegh Maaike A. , Wu Hua , Komdeur Jan 
Published: June 2022

Abstract
Life-history theory predicts trade-offs between investment in current versus future reproduction. However, many studies find no or even positive correlations among these traits. The absence of the trade-off may result from resource availability, as it influences resource allocation to different traits. In addition, since large amounts of resources require additional effort in processing, resource maintenance may affect the detection of reproductive trade-offs. Here, we carried out two breeding attempts to assess the effects of resource availability and maintenance on reproductive trade-offs for both sexes in the burying beetle (Nicrophorus vespilloides). In the first breeding attempt, we simultaneously manipulated carcass size (small versus large) and carcass preparation (non-prepared versus prepared). In the second breeding attempt, we provided parents with same-sized, non-prepared carcasses. For both breeding attempts, we monitored the main and interactive effects of carcass size and carcass preparation on parental effort and reproductive outcome. In the first breeding attempt, males gained more weight and provided more care as carcass size increased, whereas females gained more weight but did not change their care. In addition, when breeding on non-prepared versus prepared carcasses, both parents provided more care and gained more weight. In the second breeding attempt, with increased investment for the first breeding, parents did not show decreased investment for the second brood, vice versa. In contrast, males breeding on large or non-prepared carcasses gained more weight during the first breeding attempt, then provided more care in subsequent reproduction. There were no differences in subsequent female care among different treatments.

Significance statement
Resource availability and resource maintenance may affect the detection of reproductive trade-offs. Here, we simultaneously manipulated carcass size and carcass preparation to assess these effects. This is the first time that the effects of resource availability and resource maintenance on reproductive trade-offs have been separated in burying beetles. Our findings suggest that despite the increased costs of parental care and resource maintenance, parents breeding on large or non-prepared carcasses gained more benefits in terms of increased body weight by staying longer and feeding more from the carcasses. Such benefits gained during the first breeding attempt offset the costs of current reproduction to some degree and masked the reproductive trade-off between current and future reproduction in terms of parental care. These findings enhance the understanding of the effects of resource availability and maintenance on reproductive trade-offs.
Body Contouring Using a Combination of Pulsed Ultrasound and Unipolar Radio Frequency: A Prospective Pilot Study
Authors: Urdiales-Gálvez Fernando , Martín-Sánchez Sandra , Maíz-Jiménez Mónica , Viruel-Ortega Esther 
Published: June 2022

Abstract
Objective
To assess the efficacy and safety of a new non-invasive body contouring device in patients with localized fat in abdomen or in abdomen and hips. Additionally, we also evaluated the patient satisfaction with the procedure.

Methods
Prospective and non-randomized open label study. The patients underwent four sessions, separated by 1 week each, with the Alma PrimeX, a non-invasive body contouring device that combines pulsed non-focus ultrasound and a Unipolar radiofrequency. The primary end point was the mean change in fat tissue thickness, assessed by diagnostic ultrasound, from baseline to 3-months after the last treatment-session.

Results
Fifteen subjects were evaluated. As compared to pre-treatment thickness, Hodges-Lehmann median difference (95% CI) was − 85.3 (− 107.5 to − 62.0) mm, p = 0.0001; − 70.3 (− 95.0 to − 48.5) mm, p = 0.0001; − 100.0 (− 140.5 to − 49.5) mm, p = 0.0039; and − 71.8 (− 132.5 to − 23.0) mm, p = 0.0078 in infraumbilical, supraumbilical, right hip, and left hip, respectively. Pretreatment fat volume was significantly reduced from 32.9% to 31.2%, p = 0.0006. The median (interquartile range) degree of patient satisfaction was 4.0 (1.0–5.0), with 13 (86.7%) patients being “Highly satisfied” or “Satisfied” with the treatment results. The most common adverse event was discomfort, followed by erythema. All the adverse events were mild and were successfully resolved without treatment.

Conclusions
Combine therapy of a Pulsed non-focus ultrasound and Unipolar radiofrequency using the non-invasive device Alma PrimeX was an effective and safe treatment for reducing fat tissue thickness in abdomen and hips in patients with localized fat. Patients’ satisfaction with the procedure was high.

Level of Evidence IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Investigating the Safety of Multiple Body Contouring Procedures in Massive Weight Loss Patients
Authors: Ibrahiem Saad Mohamed Saad 
Published: June 2022

Abstract
Introduction
Deformities after massive weight loss are usually severe and affect many parts of the body, negatively impacting patients’ social and intimate lives. A common request of patients after massive weight loss is to treat more than one anatomical area in one surgical procedure. Advantages include a single recovery period, lower surgical costs, and faster patient satisfaction. Disadvantages may include increased need for blood transfusions, longer hospital stay, and increased risk of common complications.

Objective
The main objective of the study is to compare operative risk, hospital length of stay, complication rate, and patient satisfaction in MWLP according to the number of surgical procedures performed in the same surgical setting.

Patients and Methods
This is a retrospective case–control study of 653 MWLP who underwent multiple contouring procedures simultaneously in a single surgical procedure. All patients underwent surgery between 2016 and 2020. The patients studied were divided into 4 groups according to the number of anatomical areas operated on.

Results
A total of 1254 body contouring procedures were included in the study. Follow-up time ranged from 13 to 41 months, with a mean of 17 months. The mean age in the study was 33 years old. Women accounted for 78% of the studied population and men accounted for 22%.
The overall complication rate (major and minor) was 105 cases (16.07%) in all groups

Conclusion
Patient satisfaction was highest in patients who underwent 2–3 procedures within the same surgical setting compared to patients who underwent +3 procedures. Nevertheless, this is clinically insignificant.

Level of Evidence IV
This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
A further study comparing forward search multivariate outlier methods including ATLA with an application to clustering
Authors: Clarke Brenton R. , Grose Andrew 
Published: June 2022

AbstractThis paper makes comparisons of automated procedures for robust multivariate outlier detection through discussion and simulation. In particular, automated procedures that use the forward search along with Mahalanobis distances to identify and classify multivariate outliers subject to predefined criteria are examined. Procedures utilizing a parametric model criterion based on a$$\chi ^2$$χ2-distribution are among these, whereas the multivariate Adaptive Trimmed Likelihood Algorithm (ATLA) identifies outliers based on an objective function that is derived from the asymptotics of the location estimator assuming a multivariate normal distribution. Several criterion including size (false positive rate), sensitivity, and relative efficiency are canvassed. To illustrate relative efficiency in a multivariate setting in a new way, measures of variability of the multivariate location parameter when the underlying distribution is chosen from a multivariate generalization of the Tukey–Huber$$\epsilon $$ϵ-contamination model are used. Mean slippage models are also entertained. The simulation results here are illuminating and demonstrate there is no broadly accepted procedure that outperforms in all situations, albeit one may ascertain circumstances for which a particular method may be best if implemented. Finally the paper explores graphical monitoring for existence of clusters and the potential of classification through occurrence of multiple minima in the objective function using ATLA.
A finite element based optimization algorithm to include diffusion into the analysis of DCE-MRI
Authors: Sainz-DeMena Diego , Ye Wenfeng , Pérez María Ángeles , García-Aznar José Manuel 
Published: June 2022

AbstractPharmacokinetic (PK) models are used to extract physiological information from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) sequences. Some of the most common models employed in clinical practice, such as the standard Tofts model (STM) or the extended Tofts model (ETM), do not account for passive delivery of contrast agent (CA) through diffusion. In this work, we introduce a diffusive term based on the concept of effective diffusivity into a finite element (FE) implementation of the ETM formulation, obtaining a new formulation for the diffusion-corrected ETM (D-ETM). A gradient-based optimization algorithm is developed to characterize the vascular properties of the tumour from the CA concentration curves obtained from imaging clinical data. To test the potential of our approach, several theoretical distributions of CA concentration are generated on a benchmark problem and a real tumour geometry. The vascular properties used to generate these distributions are estimated from an inverse analysis based on both the ETM and the D-ETM approaches. The outcome of these analyses shows the limitations of the ETM to retrieve accurate parameters in the presence of diffusion. The ETM returns smoothed distributions of vascular properties, reaching unphysical values in some of them, while the D-ETM accurately depicted the heterogeneity of KTrans, v$$_{e}$$

e

and v$$_{p}$$

p

distributions (mean absolute relative difference (ARD) of 16%, 15% and 9%, respectively, for the real geometry case) keeping all their values within their physiological ranges, outperforming the ETM.
S100A1 expression characterizes terminally differentiated superficial cells in the urothelium of the murine bladder and ureter
Authors: Qasrawi Fairouz , Meuser Max , Lehnhoff Finja , Schulte Marjenna , Kispert Andreas 
Published: June 2022

AbstractThe urothelium is a stratified epithelium that lines the inner surface of the components of the urinary drainage system. It is composed of a layer of basal cells, one or several layers of intermediate cells, and a layer of large luminal superficial or umbrella cells. In the mouse, only a small set of markers is available that allows easy molecular distinction of these urothelial cell types. Here, we analyzed expression of S100A1, a member of the S100 family of calcium-binding proteins, in the urothelium of the two major organs of the murine urinary tract, the ureter and the bladder. Using RNA in situ hybridization analysis, we found exclusive expression of S100a1 mRNA in luminal cells of the ureter from embryonic day (E)17.5 onwards and of the bladder from E15.5 to adulthood. Immunofluorescence analysis showed that expression of S100A1 protein is confined to terminally differentiated superficial cells of both the ureter and bladder where it localized to the nucleus and cytoplasm. We conclude that S100A1 is a suitable marker for mature superficial cells in the urothelial lining of the drainage system of the developing and mature mouse.
Endoscopic duodenal stenting is efficient, but has higher rate of reoperations than gastrojejunostomy in palliative treatment for gastric outlet obstruction
Authors: Laitamäki Matti , Tyrväinen Tuula , Lehto Juho T. , Laukkarinen Johanna , Ukkonen Mika 
Published: June 2022

Abstract
Background
Surgical gastrojejunostomy has traditionally been the palliative treatment of choice for patients with advanced malignancies and gastric outlet obstruction syndrome. Recently, palliative endoscopic duodenal stenting has increased in popularity. We report outcomes after gastrojejunostomy and duodenal stenting when used for palliative indications.

Methods
Consecutive patients undergoing palliative gastrojejunostomy or palliative endoscopic duodenal stenting in a Finnish tertiary referral center between January 2015 and December 2020 were included. The postoperative outcomes of these two palliative interventions were compared. The main outcome measures were mortality and morbidity, rate of reoperations, postoperative oral intake ability, and length of hospital stay.

Results
A total of 88 patients, 46 (52%) patients underwent palliative gastrojejunostomy and 42 (48%) duodenal stenting. All patients had malignant disease, most typically hepatopancreatic cancer. Nineteen (44%) patients in duodenal stenting group and 4 (8.7%) patients in gastrojejunostomy group required subsequent interventions due to persisting or progressing symptoms (p < 0.001). Median delay until first oral intake was 2 days (1–24) after gastrojejunostomy and 0 days (0–3) after stenting (p < 0.001). Postoperative morbidity was 30% after gastrojejunostomy and 45% after stenting (p < 0.001). Median length of hospital stay was 7 days (1–27) after surgery and 5 days (0–20) after endoscopy (p < 0.001).

Conclusions
Patients undergoing endoscopic duodenal stenting are more able to initiate rapid oral intake and have shorter hospital stay. On the other hand, there are significantly more reoperations in stenting group. If the patient’s life expectancy is short, we recommend stenting, but for patients whose life expectancy is longer, gastrojejunostomy could be a better procedure, for the reasons mentioned above.
Role of the soluble epoxide hydrolase in the hair follicle stem cell homeostasis and hair growth
Authors: Naeem Zumer , Zukunft Sven , Günther Stephan , Liebner Stefan , Weigert Andreas , Hammock Bruce D. , Frömel Timo , Fleming Ingrid 
Published: June 2022

Abstract
Polyunsaturated fatty acids (PUFAs) are used as traditional remedies to treat hair loss, but the mechanisms underlying their beneficial effects are not well understood. Here, we explored the role of PUFA metabolites generated by the cytochrome P450/soluble epoxide hydrolase (sEH) pathway in the regulation of the hair follicle cycle. Histological analysis of the skin from wild-type and sEH−/− mice revealed that sEH deletion delayed telogen to anagen transition, and the associated activation of hair follicle stem cells. Interestingly, EdU labeling during the late anagen stage revealed that hair matrix cells from sEH−/− mice proliferated at a greater rate which translated into increased hair growth. Similar effects were observed in in vitro studies using hair follicle explants, where a sEH inhibitor was also able to augment whisker growth in follicles from wild-type mice. sEH activity in the dorsal skin was not constant but altered with the cell cycle, having the most prominent effects on levels of the linoleic acid derivatives 12,13-epoxyoctadecenoic acid (12,13-EpOME), and 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME). Fitting with this, the sEH substrate 12,13-EpOME significantly increased hair shaft growth in isolated anagen stage hair follicles, while its diol; 12,13-DiHOME, had no effect. RNA sequencing of isolated hair matrix cells implicated altered Wnt signaling in the changes associated with sEH deletion. Taken together, our data indicate that the activity of the sEH in hair follicle changes during the hair follicle cycle and impacts on two stem cell populations, i.e., hair follicle stem cells and matrix cells to affect telogen to anagen transition and hair growth.
AFM-based nanoindentation indicates an impaired cortical stiffness in the AAV-PCSK9DY atherosclerosis mouse model
Authors: Achner Leonie , Klersy Tobias , Fels Benedikt , Reinberger Tobias , Schmidt Cosima X. , Groß Natalie , Hille Susanne , Müller Oliver J. , Aherrahrou Zouhair , Kusche-Vihrog Kristina , Raasch Walter 
Published: June 2022

Abstract
Investigating atherosclerosis and endothelial dysfunction has mainly become established in genetically modified ApoE−/− or LDL-R−/− mice transgenic models. A new AAV-PCSK9DYDY mouse model with no genetic modification has now been reported as an alternative atherosclerosis model. Here, we aimed to employ this AAV-PCSK9DY mouse model to quantify the mechanical stiffness of the endothelial surface, an accepted hallmark for endothelial dysfunction and forerunner for atherosclerosis. Ten-week-old male C57BL/6 N mice were injected with AAV-PCSK9DY (0.5, 1 or 5 × 1011 VG) or saline as controls and fed with Western diet (1.25% cholesterol) for 3 months. Total cholesterol (TC) and triglycerides (TG) were measured after 6 and 12 weeks. Aortic sections were used for atomic force microscopy (AFM) measurements or histological analysis using Oil-Red-O staining. Mechanical properties of in situ endothelial cells derived from ex vivo aorta preparations were quantified using AFM-based nanoindentation. Compared to controls, an increase in plasma TC and TG and extent of atherosclerosis was demonstrated in all groups of mice in a viral load-dependent manner. Cortical stiffness of controls was 1.305 pN/nm and increased (10%) in response to viral load (≥ 0.5 × 1011 VG) and positively correlated with the aortic plaque content and plasma TC and TG. For the first time, we show changes in the mechanical properties of the endothelial surface and thus the development of endothelial dysfunction in the AAV-PCSK9DY mouse model. Our results demonstrate that this model is highly suitable and represents a good alternative to the commonly used transgenic mouse models for studying atherosclerosis and other vascular pathologies.
Interpreting and assessing confidence in network meta-analysis results: an introduction for clinicians
Authors: Yang Alan , Pechlivanoglou Petros , Aoyama Kazuyoshi 
Published: June 2022

Abstract
Purpose
We aimed to provide clinicians with introductory guidance for interpreting and assessing confidence in on Network meta-analysis (NMA) results.

Methods
We reviewed current literature on NMA and summarized key points.

Results
Network meta-analysis (NMA) is a statistical method for comparing the efficacy of three or more interventions simultaneously in a single analysis by synthesizing both direct and indirect evidence across a network of randomized clinical trials. It has become increasingly popular in healthcare, since direct evidence (head-to-head randomized clinical trials) are not always available. NMA methods are categorized as either Bayesian or frequentist, and while the two mostly provide similar results, the two approaches are theoretically different and require different interpretations of the results.

Conclusions
We recommend a careful approach to interpreting NMA results and the validity of an NMA depends on its underlying statistical assumptions and the quality of the evidence used in the NMA.