bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twice-daily insulin degludec/insulin aspart effectively improved morning and evening glucose levels and quality of life in patients previously treated with premixed insulin: an observational study
Authors: Fujimoto Kanta , Iwakura Toshio , Aburaya Megumi , Matsuoka Naoki 
Published: August 2018

Abstract
Background
Previous studies comparing insulin degludec/insulin aspart (IDegAsp) with premixed insulin twice daily among insulin users with type 2 diabetes have not thoroughly investigated differences in the glucose variability and psychological evaluations related to insulin regimen changes. We investigated changes in the daily and day-to-day glucose variability and quality of life (QOL) related to insulin use in patients with type 2 diabetes during a switch from premixed insulin preparations comprising either human insulin (BHI30) or insulin aspart (BIAsp30) to IDegAsp twice daily.

Methods
In this prospective observational study, 22 subjects (BHI30:BIAsp30 = 12:10) self-measured their blood glucose levels every morning, and before and after all meals each week. Premixed insulin was administered for the first 2 months, followed by IDegAsp for the next 2 months. Efficacy measures were evaluated during the last month or last day of both phases.

Results
The mean blood glucose levels (175.5 vs. 163.0 mg/dL; P = 0.004) and the M-values (53.9 vs. 27.6; P = 0.049) were significantly lower in the IDegAsp phase. However, no differences in the standard deviations of morning fasting glucose levels were observed between phases (premixed vs. IDegAsp, 20.0 vs. 19.3 mg/dL; P = 0.343). Compared to the premixed phase, the before-breakfast (145.3 vs. 126.0 mg/dL; P < 0.001), after-breakfast (190.3 vs. 170.7 mg/dL; P = 0.001), before-dinner (153.0 vs. 140.1 mg/dL; P  = 0.007), and after-dinner glucose levels (198.7 vs. 181.4 mg/dL; P = 0.018) were lower in the IDegAsp phase. However, the before-lunch (150.8 vs. 148.2 mg/dL; P  = 0.329) and after-lunch glucose levels (214.7 vs. 211.4 mg/dL; P = 0.308) did not significantly differ between phases. Regarding QOL, the total and therapy-related feeling Insulin Therapy Related-QOL (ITR-QOL) questionnaire scores favored IDegAsp, as did the ITR-QOL at Night questionnaire subscale score of glycemic control before breakfast.

Conclusions
Although the day-to-day variability of morning fasting glucose levels did not change, switching to IDegAsp improved daily glucose level variability, the morning and evening glucose control and QOL among patients treated with premixed insulin.
Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000021939. Prospectively registered 18 April 2016
Rise of the machines? Machine learning approaches and mental health: opportunities and challenges
Authors: Tiffin Paul A. , Paton Lewis W. 
Published: August 2018

SummaryMachine learning methods are being increasingly applied to physical healthcare. In this article we describe some of the potential benefits, challenges and limitations of this approach in a mental health context. We provide a number of examples where machine learning could add value beyond conventional statistical modelling.Declaration of interestNone.
Structural and Functional Biology of Aldo-Keto Reductase Steroid-Transforming Enzymes
Authors: Penning Trevor M , Wangtrakuldee Phumvadee , Auchus Richard J 
Published: August 2018

AbstractAldo-keto reductases (AKRs) are monomeric NAD(P)(H)-dependent oxidoreductases that play pivotal roles in the biosynthesis and metabolism of steroids in humans. AKR1C enzymes acting as 3-ketosteroid, 17-ketosteroid, and 20-ketosteroid reductases are involved in the prereceptor regulation of ligands for the androgen, estrogen, and progesterone receptors and are considered drug targets to treat steroid hormone–dependent malignancies and endocrine disorders. In contrast, AKR1D1 is the only known steroid 5β-reductase and is essential for bile-acid biosynthesis, the generation of ligands for the farnesoid X receptor, and the 5β-dihydrosteroids that have their own biological activity. In this review we discuss the crystal structures of these AKRs, their kinetic and catalytic mechanisms, AKR genomics (gene expression, splice variants, polymorphic variants, and inherited genetic deficiencies), distribution in steroid target tissues, roles in steroid hormone action and disease, and inhibitor design.
Aldosterone LC-MS/MS Assay-Specific Threshold Values in Screening and Confirmatory Testing for Primary Aldosteronism
Authors: Guo Zeng , Poglitsch Marko , McWhinney Brett C , Ungerer Jacobus P J , Ahmed Ashraf H , Gordon Richard D , Wolley Martin , Stowasser Michael 
Published: August 2018

Abstract

Context
Current threshold values for primary aldosteronism (PA) diagnostic testing are based on measuring aldosterone (PAC) using immunoassays. Quantification of PAC by liquid chromatography-tandem mass spectrometry (LC-MS/MS) yields lower values.

Objective
To compare aldosterone measurement by radioimmunoassay (RIA) with LC-MS/MS and evaluate performances of proposed LC-MS/MS–specific cutoffs for PA screening and confirmatory testing.

Patients and Intervention
Forty-one patients underwent aldosterone/renin ratio (ARR) testing to screen for, and fludrocortisone suppression testing (FST) to confirm or exclude, PA. Renin (DRC) was measured by chemiluminescent immunoassay.

Results
Median serum PACLC-MS/MS was 27.8% lower (P &lt; 0.05) than plasma PACRIA in 164 pairs of FST samples. A positive correlation (Spearman coefficient, 0.894, P &lt; 0.01; Pearson r coefficient, 0.861, P &lt; 0.01) was observed between the two assays. Thirty-seven patients showed consistent FST diagnoses (29 positive, 8 negative), whereas four showed inconsistent FSTs by the two assays. Good agreement (κ coefficient, 0.736; P &lt; 0.01) was observed between the current FST diagnostic PACRIA cutoff of 165 pmol/L and the proposed PACLC-MS/MS cutoff of 133 pmol/L. Among 37 patients with consistent FST results, no differences were observed in sensitivity (89.7% vs 93.1%) or specificity (87.5% vs 87.5%) for PA screening between the current ARR cutoff of 70 pmol/mU (PACRIA/DRC) and the proposed cutoff of 55 pmol/mU (PACLC-MS/MS/DRC).

Conclusions
Adjustment of the current cutoffs for PA diagnostic testing is necessary if PAC is measured by LC-MS/MS. Our preliminary results suggest that the proposed LC-MS/MS cutoffs for ARR and FST perform as well as current RIA cutoffs.
Serum Human Chorionic Gonadotropin Among Women With and Without Obesity After Single Embryo Transfers
Authors: Brady Paula C , Farland Leslie V , Ginsburg Elizabeth S 
Published: August 2018

Abstract

Context
Serum human chorionic gonadotropin (hCG) levels are essential for diagnosing and monitoring early pregnancy. Obesity is a health care epidemic; however, the performance of this vital serum hormone in women with an elevated body mass index (BMI) is unknown.

Objective
To investigate the association of BMI with serum hCG values and rate of hCG increase.

Design
Retrospective cohort study.

Setting
University-based infertility clinic.

Patients
Women undergoing fresh vs frozen in vitro fertilization cycles with single-day three or five embryo transfers resulting in singleton live births (≥24 weeks’ gestational age) from 2008 to 2015.

Intervention(s)
None.

Main Outcome Measure(s)
The initial hCG (mIU/mL, 16 days after oocyte retrieval) and 2-day percentage of hCG increases among BMI categories were compared using multivariable linear and logistic regression, adjusted a priori for the day of embryo transfer.

Results
The initial serum hCG values correlated inversely with the BMI (P &lt; 0.0001, test for trend). Low initial hCG values (&lt;100 mIU/mL) were significantly more common across increasing BMI classes, from 1.4% of normal weight patients to 15.6% of those with a BMI ≥40 kg/m2 (P = 0.001, test for trend). The mean 2-day hCG increases were similar and normal (≥53%) across the BMI groups.

Conclusions
Patients with obesity achieving live births had statistically significantly lower initial serum hCG values compared with patients who were nonobese. However, the mean 2-day percentage of increases in hCG were similar across BMI categories. The initial hCG values might lack sensitivity for live births in patients with obesity. The rate of hCG increase remains the mainstay of monitoring very early pregnancies after in vitro fertilization. Future studies should investigate whether serum analyte ranges should be adjusted according to the BMI.
Termination of cell-type specification gene programs by the miR-183 cluster determines the population sizes of low-threshold mechanosensitive neurons
Authors: Peng Changgeng , Furlan Alessandro , Zhang Ming-Dong , Su Jie , Lübke Moritz , Lönnerberg Peter , Abdo Hind , Sontheimer Jana , Sundström Erik , Ernfors Patrik 
Published: August 2018

ABSTRACT
Touch and mechanical sensations require the development of several different kinds of sensory neurons dedicated to respond to certain types of mechanical stimuli. The transcription factor Shox2 (short stature homeobox 2) is involved in the generation of TRKB+ low-threshold mechanoreceptors (LTMRs), but mechanisms terminating this program and allowing alternative fates are unknown. Here, we show that the conditional loss of the miR-183-96-182 cluster in mouse leads to a failure of extinction of Shox2 during development and an increase in the proportion of Aδ LTMRs (TRKB+/NECAB2+) neurons at the expense of Aβ slowly adapting (SA)-LTMRs (TRKC+/Runx3−) neurons. Conversely, overexpression of miR-183 cluster that represses Shox2 expression, or loss of Shox2, both increase the Aβ SA-LTMRs population at the expense of Aδ LTMRs. Our results suggest that the miR-183 cluster determines the timing of Shox2 expression by direct targeting during development, and through this determines the population sizes of Aδ LTMRs and Aβ SA-LTMRs.
Walking in Minimalist Shoes Is Effective for Strengthening Foot Muscles
Authors: RIDGE SARAH T. , OLSEN MARK T. , BRUENING DUSTIN A. , JURGENSMEIER KEVIN , GRIFFIN DAVID , DAVIS IRENE S. , JOHNSON A. WAYNE 
Published: August 2018

ABSTRACT

Introduction
Weakness of foot muscles may contribute to a variety of loading-related injuries. Supportive footwear may contribute to intrinsic foot muscle weakness by reducing the muscles’ role in locomotion (e.g., absorbing forces and controlling motion). Increased stimulus to the foot muscles can be provided through a variety of mechanisms, including minimalist footwear and directed exercise.

Purpose
To determine the effect of walking in minimalist footwear or performing foot strengthening exercises on foot muscle size and strength.

Methods
Fifty-seven runners were randomly assigned to one of three groups—minimalist shoe walking (MSW), foot strengthening (FS) exercise, or control (C). All groups maintained their prestudy running mileage throughout the study. The MSW group walked in provided footwear, increasing weekly the number of steps per day taken in the shoes. The FS group performed a set of progressive resistance exercises at least 5 d·wk−1. Foot muscle strength (via custom dynamometers) and size (via ultrasound) were measured at the beginning (week 0), middle (week 4), and end (week 8) of the study. Mixed model ANOVA were run to determine if the interventions had differing effects on the groups.

Results
There were significant group–time interactions for all muscle size and strength measurements. All muscle sizes and strength increased significantly from weeks 0 to 8 in the FS and MSW groups, whereas there were no changes in the C group. Some muscles increased in size by week 4 in the FS and MSW groups.

Conclusions
Minimalist shoe walking is as effective as foot strengthening exercises in increasing foot muscle size and strength. The convenience of changing footwear rather than performing specific exercises may result in greater compliance.
Analgesia linked to Nav1.7 loss of function requires µ- and δ-opioid receptors
Authors: Pereira Vanessa , Millet Queensta , Aramburu Jose , Lopez-Rodriguez Cristina , Gaveriaux-Ruff Claire , Wood John N. 
Published: August 2018

Background: Functional deletion of the Scn9a (sodium voltage-gated channel alpha subunit 9) gene encoding sodium channel Nav1.7 makes humans and mice pain-free. Opioid signalling contributes to this analgesic state. We have used pharmacological and genetic approaches to identify the opioid receptors involved in this form of analgesia. We also examined the regulation of proenkephalin expression by the transcription factor Nfat5 that binds upstream of the Penk gene. Methods: We used specific µ-, δ- and κ-opioid receptor antagonists alone or in combination to examine which opioid receptors were necessary for Nav1.7 loss-associated analgesia in mouse behavioural assays of thermal pain. We also used µ- and δ-opioid receptor null mutant mice alone and in combination in behavioural assays to examine the role of these receptors in Nav1.7 knockouts pain free phenotype. Finally, we examined the levels of Penk mRNA in Nfat5-null mutant mice, as this transcription factor binds to consensus sequences upstream of the Penk gene. Results: The pharmacological block or deletion of both µ- and δ-opioid receptors was required to abolish Nav1.7-null opioid-related analgesia. κ-opioid receptor antagonists were without effect. Enkephalins encoded by the Penk gene are upregulated in Nav1.7 nulls. Deleting Nfat5, a transcription factor with binding motifs upstream of Penk, induces the same level of enkephalin mRNA expression as found in Nav1.7 nulls, but without consequent analgesia. These data confirm that a combination of events linked to Scn9a gene loss is required for analgesia. Higher levels of endogenous enkephalins, potentiated opioid receptors, diminished electrical excitability and loss of neurotransmitter release together contribute to the analgesic phenotype found in Nav1.7-null mouse and human mutants. Conclusions: These observations help explain the failure of Nav1.7 channel blockers alone to produce analgesia and suggest new routes for analgesic drug development.
Hemiarthroplasty compared with total hip arthroplasty in fractured neck of femur: a shift in national practice?
Authors: Khan AM , Rafferty M , Daurka JS 
Published: August 2018

Introduction The aim of this study was to determine the trends in national practice regarding total hip arthroplasty compared with hemiarthroplasty in fractured neck of femur between 2010 and 2016. Materials and methods A retrospective review was conducted of NHS Digital data (England) between 2010 and 2016. ‘Emergency’ neck of femur fracture admissions, hemiarthroplasties and total hip arthroplasties were included. Elective total hip arthroplasties, revisions and prostheses relocations were excluded. Annual percentages for each operation were calculated. Trends were tabulated and displayed graphically for analysis. Results The total number of emergency neck of femur diagnoses was 257,789. Total hip arthroplasty was performed in 2217, 2737, 3305, 3686, 3670 and 3825 patients and hemiarthroplasty was performed in 21,335, 21,744, 21,115, 21,798, 21,804 and 22,163 patients for each year between 2011 and 2016, respectively. The rate of change for total hip arthroplasty slowed from 24.54% increase/year (2011–2013) to 5.24% increase/year (2013–2016). Uncemented arthroplasties decreased over the same time period. Discussion Increasing numbers of total hip arthroplasties are conducted for hip fractures; however, this trend has slowed since 2013. Possible explanations include all eligible fractures being treated with total hip arthroplasty, trauma surgeon preference for hemiarthroplasty due to lower surgical specialism or publication of individual surgeon data (National Joint Registry) which may lead to surgeons favouring hemiarthroplasties which have a lower complication rate compared to elective total hip arthroplasties.
Proteomic Discovery and Validation of the Confounding Effect of Heparin Administration on the Analysis of Candidate Cardiovascular Biomarkers
Authors: Beck Hans C , Jensen Lisette O , Gils Charlotte , Ilondo Albertine M M , Frydland Martin , Hassager Christian , Møller-Helgestad Ole K , Møller Jacob E , Rasmussen Lars M 
Published: August 2018

Abstract

BACKGROUND
Several plasma proteins have been suggested as markers for a variety of cardiovascular conditions but fail to qualify in independent patient cohorts. This may relate to interference of medication on plasma protein concentrations. We used proteomics to identify plasma proteins that changed in concentration with heparin administration and therefore potentially may confound their evaluation as biomarkers in situations in which heparin is used.

METHODS
We used a proteomic approach based on isobaric tagging and nano-LC-MS/MS analysis to quantify several hundred proteins in a discovery study in which individual plasma samples from 9 patients at intravascular ultrasound follow-up 12 months after an acute myocardial infarction before heparin administration and 2, 15, and 60 min after heparin administration; we validated our findings in 500 individual plasma samples obtained at admission from patients with suspected ST segment elevation myocardial infarction (STEMI), of whom 363 were treated with heparin before admission.

RESULTS
In the discovery study, 25 of 653 identified plasma proteins displayed a changed concentration after heparin administration (Bonferroni-corrected P value at P &lt; 7.66 × 10−5). Fourteen of the proteins changed significantly among heparin-treated patients in the validation study (nominal significance level of P &lt; 6.92 × 10−5). Among heparin-affected proteins in both the discovery study and the validation study were midkine, spondin 1, secreted frizzled-like protein 1, lipoprotein lipase, and follistatin, all previously associated with STEMI.

CONCLUSIONS
Medications such as heparin administration given before blood sampling may confound biomarker discovery and should be carefully considered in such studies.
Comparison between High-Sensitivity Cardiac Troponin T and Cardiac Troponin I in a Large General Population Cohort
Authors: Welsh Paul , Preiss David , Shah Anoop S V , McAllister David , Briggs Andrew , Boachie Charles , McConnachie Alex , Hayward Caroline , Padmanabhan Sandosh , Welsh Claire , Woodward Mark , Campbell Archie , Porteous David , Mills Nicholas L , Sattar Naveed 
Published: August 2018

Abstract

BACKGROUND
Few data compare cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in a general population. We sought to evaluate the distribution and association between cTnT, cTnI, and cardiovascular risk factors in a large general population cohort.

METHODS
High-sensitivity cTnT and cTnI were measured in serum from 19501 individuals in the Generation Scotland Scottish Family Health Study. Associations with cardiovascular risk factors were compared using age- and sex-adjusted regression. Observed age- and sex-stratified 99th centiles were compared with 99th centiles for cTnT (men, 15.5 ng/L; women, 9.0 ng/L) and cTnI (men, 34.2 ng/L; women, 15.6 ng/L) used in clinical practice.

RESULTS
cTnT and cTnI concentrations were detectable in 53.3% and 74.8% of participants, respectively, and were modestly correlated in unadjusted analyses (R2 = 21.3%) and only weakly correlated after adjusting for age and sex (R2 = 9.5%). Cardiovascular risk factors were associated with both troponins, but in age- and sex-adjusted analyses, cTnI was more strongly associated with age, male sex, body mass index, and systolic blood pressure (P &lt; 0.0001 for all vs cTnT). cTnT was more strongly associated with diabetes (P &lt; 0.0001 vs cTnI). The observed 99th centiles were broadly consistent with recommended 99th centiles in younger men and women. After the age of 60 years, observed 99th centiles increased substantially for cTnT, and beyond 70 years of age, the 99th centiles approximately doubled for both troponins.

CONCLUSIONS
In the general population, cTnT and cTnI concentrations are weakly correlated and are differentially associated with cardiovascular risk factors. The 99th centiles currently in use are broadly appropriate for men and women up to but not beyond the age of 60 years.
Narrative ethics and cultural analysis. Insolvency stories and moral debt relief
Authors: Meyer Silke 
Published: August 2018

AbstractIn this article and with the example of debt stories, I discuss the theory of narrative ethics and the hypothesis that a person needs a story to make sense of his or her life. Knowing that narrators are able to correct rupture and deviance through the right kind of story, I conclude that a socially and discursively compatible debt story can compensate for the experience of social exclusion. Based on interview material with debtors, I can show how narrative structure becomes a key instrument in presenting a debt story successfully: conversion, educational or underdog stories enable storytellers to claim agency and take control over the narrative representation of their lives
Changes in External Load When Modifying Rules of 5-on-5 Scrimmage Situations in Elite Basketball
Authors: Vazquez-Guerrero Jairo , Reche Xavi , Cos Francesc , Casamichana David , Sampaio Jaime 
Published: August 2018

Abstract
Vazquez-Guerrero, J, Reche, X, Cos, F, Casamichana, D, and Sampaio, J. Changes in external load when modifying rules of 5-on- 5 scrimmage situations in elite basketball. J Strength Cond Res 34(11): 3217–3224, 2020—Constraining tasks are very frequent during the team sports training process; however, most of the effects of these coaching decisions are unknown, which leads to less controlled performing environments, with less chances to promote improvements. The aim of this study was to determine the effects of modifying rules of 5-a-side scrimmage on the physical performance of professional basketball players. Data were collected from 12 elite male players (age, 29.6 ± 4.5 years; height, 1.99 ± 9.6 cm; body mass, 92.1 ± 11.9 kg) from the Spanish first Division of Basketball during thirty-three 5-on-5 scrimmage situations over a 18-week period. Physical demands were assessed using WIMU PRO Local Positioning System (Realtrack Systems, Almeria, Spain) and included total and speed-ranged distance covered, player load, peak speed, number of high-intensity actions, number of total and high-intensity accelerations and decelerations, and peak acceleration. A repeated-measures analysis of variance was used to test the differences in all variables, considering playing in half-court (HALF), half-court and transition (HTRAN), and full-court (FULL) conditions for the 5-on-5 scrimmage drill. Results showed that during the HALF condition, there was less distance covered (effect size [ES] = 3.55), lower peak speeds (ES = 3.00), less player load (ES = 2.79), lesser number of high-intensity actions (ES = 1.45), and lesser number of high-intensity accelerations (ES = 1.44) and decelerations (ES = 1.31) than in FULL. In HTRAN, players covered more distance (ES = 2.42), presented higher player load (ES = 1.88), higher intensity actions (ES = 1.02), and peak speed (ES = 4.22) than in HALF. In conclusion, physical demands can be modulated changing the rules and court size using 5-on-5 scrimmage situations, and this factor should be taken into account when designing training drills and when fine-tuning periodization.