bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial
Authors: Deehan Edward C. , Colin-Ramirez Eloisa , Triador Lucila , Madsen Karen L. , Prado Carla M. , Field Catherine J. , Ball Geoff D. C. , Tan Qiming , Orsso Camila , Dinu Irina , Pakseresht Mohammadreza , Rubin Daniela , Sharma Arya M. , Tun Hein , Walter Jens , Newgard Christopher B. , Freemark Michael , Wine Eytan , Haqq Andrea M. 
Published: February 2021

Abstract
Background
Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome.

Methods
This is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12–18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids.

Discussion
This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention.

Trial registration
ClinicalTrials.gov NCT04578652. Registered on 8 October 2020.
A virtual alternative to molecular model sets: a beginners’ guide to constructing and visualizing molecules in open-source molecular graphics software
Authors: Phankingthongkum Siripreeya , Limpanuparb Taweetham 
Published: February 2021

Abstract
Objective
The application of molecular graphics software as a simple and free alternative to molecular model sets for introductory-level chemistry learners is presented.

Results
Based on either Avogadro or IQmol, we proposed four sets of tasks for students, building basic molecular geometries, visualizing orbitals and densities, predicting polarity of molecules and matching 3D structures with bond-line structures. These topics are typically covered in general chemistry for first-year undergraduate students. Detailed step-by-step procedures are provided for all tasks for both programs so that instructors and students can adopt one of the two programs in their teaching and learning as an alternative to molecular model sets.
CERTL reduces C16 ceramide, amyloid-β levels, and inflammation in a model of Alzheimer’s disease
Authors: Crivelli Simone M. , Luo Qian , Stevens Jo A.A. , Giovagnoni Caterina , van Kruining Daan , Bode Gerard , den Hoedt Sandra , Hobo Barbara , Scheithauer Anna-Lena , Walter Jochen , Mulder Monique T. , Exley Christopher , Mold Matthew , Mielke Michelle M. , De Vries Helga E. , Wouters Kristiaan , van den Hove Daniel L. A. , Berkes Dusan , Ledesma María Dolores , Verhaagen Joost , Losen Mario , Bieberich Erhard , Martinez-Martinez Pilar 
Published: February 2021

AbstractBackgroundDysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer’s disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain.MethodsA plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTLwith amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERTLprotein was employed to study interaction of CERTLwith amyloid-β (Aβ), Aβ aggregation process in presence of CERTL, and the resulting changes in Aβ toxicity in neuroblastoma cells. CERTLwas overexpressed in neurons by adeno-associated virus (AAV) in a mouse model of familial AD (5xFAD). Ten weeks after transduction, animals were challenged with behavior tests for memory, anxiety, and locomotion. At week 12, brains were investigated for sphingolipid levels by mass spectrometry, plaques, and neuroinflammation by immunohistochemistry, gene expression, and/or immunoassay.ResultsHere, we report that CERTLbinds to APP, modifies Aβ aggregation, and reduces Aβ neurotoxicity in vitro. Furthermore, we show that intracortical injection of AAV, mediating the expression of CERTL, decreases levels of ceramide d18:1/16:0 and increases sphingomyelin levels in the brain of male 5xFAD mice. CERTLin vivo over-expression has a mild effect on animal locomotion, decreases Aβ formation, and modulates microglia by decreasing their pro-inflammatory phenotype.ConclusionOur results demonstrate a crucial role of CERTLin regulating ceramide levels in the brain, in amyloid plaque formation and neuroinflammation, thereby opening research avenues for therapeutic targets of AD and other neurodegenerative diseases.
Bayesian multilevel model on maternal mortality in Ethiopia
Authors: Jabessa Shibiru , Jabessa Dabala 
Published: February 2021

AbstractMaternal mortality is one of the socio-economic problems and widely considered a serious indicator of the quality of a health. Ethiopia is considered to be one of the top six sub-Saharan countries with severe maternal mortality. The objective of this study was to investigate the effects of the Demographic and Socio-economic determinant factors of maternal mortality in Ethiopia. Data from the 2016 Ethiopia Demographic and Health Survey indicated that the sample of women (15–49) was (n = 10,103). The Bayesian multilevel we were used to explore the major risk factors and regional variations in maternal mortality in Ethiopia. Markov chain Monte Carlo methods with non-informative priors have been applied. The Deviance Information Criterion model selection criteria were used to select the appropriate model. The analysis result, 145 (1.43%) mothers were died due to pregnancy. Using model selection criteria Bayesian multilevel random coefficient was found to be appropriate. With this model, Age of mother, marital status, number of living children, wealth index and Education are found to be the significant determinants of maternal mortality in Ethiopia. The study indicated that there was within and between regional variations in maternal mortality. Inference is the fully Bayesian multilevel model based on recent Markov chain Monte Carlo techniques. The socioeconomic, demographic and environmental determinants included in the study were found to be statistically significant. The result of the Bayesian multilevel model in this study has shown that educational attainment, wealth index, an age of mother, status and number of living children was a significant factor of maternal mortality.
A comparison of standard occupational therapy versus early enhanced occupation-based therapy in a medical/surgical intensive care unit: study protocol for a single site feasibility trial (EFFORT-ICU)
Authors: Rapolthy-Beck Andrea , Fleming Jennifer , Turpin Merrill , Sosnowski Kellie , Dullaway Simone , White Hayden 
Published: February 2021

AbstractBackgroundAdmissions to intensive care units (ICUs) are increasing due to an ageing population, and rising incidence of cardiac and respiratory disease. With advances in medical care, more patients are surviving an initial stay in critical care; however, they can experience ongoing health and cognitive limitations that may influence return to baseline function up to a year post-admission. Recent research has focused on the introduction of early rehabilitation within the ICU to reduce long-term physical and cognitive complications. The aim of this study is to explore the feasibility and impact of providing early enhanced occupation-based therapy, including cognitive stimulation and activities of daily living, to patients in intensive care.MethodsThis study involves a single site randomised-controlled feasibility trial comparing standard occupational therapy care to an early enhanced occupation-based therapy. Thirty mechanically ventilated ICU patients will be recruited and randomly allocated to the intervention or control group. The primary outcome measure is the Functional Independence Measure (FIM), and secondary measures include the Modified Barthel Index (MBI), Montreal Cognitive Assessment (MoCA), grip strength, Hospital Anxiety and Depression Scale (HADS) and Short-Form 36 Health survey (SF-36). Measures will be collected by a blind assessor at discharge from intensive care, hospital discharge and a 90-day follow-up. Daily outcome measures including the Glasgow Coma Scale (GCS), Richmond Agitation and Sedation Scale (RASS) and Confusion Assessment Measure for intensive care units (CAM-ICU) will be taken prior to treatment. Participants in the intervention group will receive daily a maximum of up to 60-min sessions with an occupational therapist involving cognitive and functional activities such as self-care and grooming. At the follow-up, intervention group participants will be interviewed to gain user perspectives of the intervention. Feasibility data including recruitment and retention rates will be summarised descriptively. Parametric tests will compare outcomes between groups. Interview data will be thematically analysed.DiscussionThis trial will provide information about the feasibility of investigating how occupational therapy interventions in ICU influence longer term outcomes. It seeks to inform the design of a phase III multicentre trial of occupational therapy in critical care general medical intensive care units.Trial registrationAustralia New Zealand Clinical Trials Registry (ANZCTR):ACTRN12618000374268; prospectively registered on 13 March 2018/https://www.anzctr.org.auTrial funding: Metro South Health Research Support Scheme Postgraduate Scholarship
Management of iron deficiency anemia in hemodialysis patients based on mean corpuscular volume
Authors: Onda Kumiko , Koyama Teruo , Kobayashi Sanae , Ishii Yoji , Ohashi Kazuo 
Published: February 2021

Abstract
Background
To manage the anemic status in hemodialysis (HD) patients, a well-balanced combination therapy based on the use of erythropoiesis-stimulating agents (ESAs) and iron supplementation is essential. Serum ferritin level and transferrin saturation rate (TSAT) are the current standard tests for screening iron deficiency status. However, these are not included in frequently checked regular blood measurements in many HD centers. Other parameters that could predict a hemoglobin (Hb) increase response from iron supplementation have yet to be established. To determine a frequently checked and regularly measured biomarker for predicting iron deficiency status, this study investigated the value of mean corpuscular volume (MCV) as a clinical parameter for HD patients receiving intravenous iron supplementation (Fe-IV) therapy.

Methods and results
One hundred thirty four HD patients, 88 non-HD patients with anemia, and 50 HD patients on Fe-IV therapy from the Nozatomon clinic were assessed. Comparison of MCV values of anemic HD patients and anemic non-chronic kidney disease (CKD) patients showed that anemic HD patients had significantly higher MCV values (93.9 ± 7.3 fL) compared with anemic non-CKD patients (82.8 ± 8.8fL). Fifty HD patients, who received Fe-IV therapy at ten consecutive HD sessions (inclusion criteria: Hb ≤ 12.0 g/dL, TSAT < 20%, and serum ferritin < 100 ng/mL) showed a rapid increase during the Fe-IV period in MCV, Hb, and TSAT levels. After the completion of the Fe-IV therapy, MCV persisted at the increased levels, whereas Hb levels further increased and peaked at 1 month with a gradual decline after, largely influenced by ESA dosage reductions. The 50 patients were divided into three groups according to the MCV levels obtained immediately prior to the Fe-IV therapy (MCV ≤ 85 fL, 85 fL < MCV ≤ 90 fL, MCV > 90 fL), and Hb changes at 50 days after the initiation of the Fe-IV therapy were compared. All the patients in the MCV ≤ 85 fL group and most of the patients in the 85 fL < MCV ≤ 90 fL group showed linear and consistent Hb increase during the 50-day period. In marked contrast, patients in the MCV > 90 fL group showed dispersed trends in their Hb increase. The present study also revealed that successful ESA dosage reduction could be achieved after the Fe-IV therapy in both the MCV ≤ 85 fL and 85 fL < MCV ≤ 90 fL groups.

Conclusions
The present study underscored the value of MCV in perceiving iron deficiency status as well as predicting iron-based therapeutic response in HD patients.
Glucose-level dependent brain hypometabolism in type 2 diabetes mellitus and obesity
Authors: Képes Z. , Aranyi Cs. , Forgács A. , Nagy F. , Kukuts K. , Hascsi Zs. , Esze R. , Somodi S. , Káplár M. , Varga J. , Emri M. , Garai I. 
Published: February 2021

Abstract
Background
Metabolic syndrome and its individual components lead to wide-ranging consequences, many of which affect the central nervous system. In this study, we compared the [18F]FDG regional brain metabolic pattern of participants with type 2 diabetes mellitus (T2DM) and non-DM obese individuals.

Methods
In our prospective study, 51 patients with controlled T2DM (ages 50.6 ± 8.0 years) and 45 non-DM obese participants (ages 52.0 ± 9.6 years) were enrolled. Glucose levels measured before PET/CT examination (pre-PET glucose) as well as laboratory parameters assessing glucose and lipid status were determined. NeuroQ application (NeuroQTM 3.6, Syntermed, Philips) was used to evaluate regional brain metabolic differences. [18F]FDG PET/CT (AnyScan PC, Mediso) scans, estimating brain metabolism, were transformed to MNI152 brain map after T1 registration and used for SPM-based group comparison of brain metabolism corrected for pre-PET glucose, and correlation analysis with laboratory parameters.

Results
NeuroQ analysis did not reveal significant regional metabolic defects in either group. Voxel-based group comparison revealed significantly (PFWE<0.05) decreased metabolism in the region of the precuneus and in the right superior frontal gyrus (rSFG) in the diabetic group as compared to the obese patients. Data analysis corrected for pre-PET glucose level showed a hypometabolic difference only in the rSFG in T2DM. Voxel-based correlation analysis showed significant negative correlation of the metabolism in the following brain regions with pre-PET glucose in diabetes: precuneus, left posterior orbital gyrus, right calcarine cortex and right orbital part of inferior frontal gyrus; whilst in the obese group only the right rolandic (pericentral) operculum proved to be sensitive to pre-PET glucose level.

Conclusions
To our knowledge, this is the first study to perform pre-PET glucose level corrected comparative analysis of brain metabolism in T2DM and obesity. We also examined the pre-PET glucose level dependency of regional cerebral metabolism in the two groups separately. Large-scale future studies are warranted to perform further correlation analysis with the aim of determining the effects of metabolic disturbances on brain metabolism.
Sex estimation based on the anthropometric measurements of thyroid cartilage using discriminant analysis
Authors: Cameriere Roberto , Zolotenkova Galina V. , Kuznetsov Igor A. , Scendoni Roberto , Pigolkin Yuri I. 
Published: February 2021

AbstractBackgroundThe morphometric analysis of the individual bones of the human skeleton can be used to estimate the sex of unidentified corpses. Our aims were as follows: to test whether thyroid cartilage can be used for forensic purposes as a predictor of biological sex; to establish the level of sexual dimorphism of the thyroid cartilage in a sample of adult subjects from a population of European Russia; and to test the accuracy of the morphometric parameters obtained from the thyroid cartilage.ResultsThe thyroid cartilage from 100 adults of known age (50 males and 50 females) was obtained during forensic examination; morphometric tests were conducted using Vernier Digital ROKTOOLS ABS DIN 862 0-200/6 inch with measurement accuracy ± 0.01 mm. The measured parameters wereN= 31 for each subject. Intra- and inter-observer reproducibility was tested. Multivariate statistical analysis was applied to the measurements. To check the data set for normal distribution, the Kolmogorov-Smirnov test was used. Finally, to estimate the sex of the observed individuals, a stepwise discriminant analysis was conducted, using the Wilks’ lambda selection method. The most significant parameters were the outer distance between bases of inferior horn; the inner distance between distal ends of inferior horns; distance between distal ends of left superior and inferior horns; left superior horn length (distance between left superior horn distal end and base); distance between superior and inferior notches; thyroid angle; left lamina height (vertical line along left lamina middle); horizontal distance between anterior intermedium line and the right lamina posterior edge; distance between inferior thyroid notch and line connecting left and right thyroid laminae; and left superior horn thickness at mid-line. The stepwise discriminant analysis resulted in an equation with ten parameters.ConclusionsThe results of the current study indicated that in the European Russian population, the equation obtained in the stepwise discriminant analysis makes it possible to predict sex with a probability of 100% on the validation set. On the test set, the resultant accuracy was 100% for females and 100% for males. Our findings confirm the scientific evidence that the thyroid cartilage has a pronounced sexual dimorphism.
Seasonal shape variations, ontogenetic shape changes, and sexual dimorphism in a population of land isopod Porcellionides pruinosus: a geometric morphometric study
Authors: Ismail Tarek G. 
Published: February 2021

AbstractBackgroundIsopods shape features are sensitive and respond to several selective pressures which may result in variations of these features. These pressures might reflect the heterogeneity of the environment where an animal lives. Land isopodsPorcellionides pruinosuswere collected from an agricultural field. Landmarks geometric morphometrics was applied to evaluate its shape changes during two different seasons. The present work aims to (i) assess and characterize morphological changes in body shape ofP. pruinosusas a response to seasonal variations, (ii) determine differences in the body shape during ontogeny, (iii) examine the effect of intraspecific allometry to interpret the observed variations in the species, and (iv) clarify whether the body shape ofP. pruinosuscan be used as a sexual differentiating trait.ResultsJuveniles showed no seasonal variations in the body shape, which were detected among adults, females and males as shown by PCA, DFA, and MANOVA.The adult winter forms have large bodies, small heads, broad pereons, and short but wide telsons. The adult summer forms have small slender bodies, slightly stretched heads, and relatively long telsons. Juveniles’ growth to adulthood showed body shape changes in the head and pereon, that include shrank of the head in the anteroposterior direction and its level became slightly lower than the body. The pereon becomes broader and the two anterolateral projections of the first pereonite extend anteriorly, reaching a little beyond the posterior margin of the eyes. Present species showed a shape sexual dimorphism which includes the broader body and more convex pereon in females and a small waist between the second and third pleonites in males. Shape sexual dimorphism was attributed to reproductive activity. Both allometric trajectories of juveniles and adults (ontogenetic allometry) and of sexes (static allometry) were parallel.ConclusionsThe landmark geometric morphometric technique was able to reveal the seasonal shape variations in terrestrial isopodP. pruinosus. Also, this method provides information about shape variations between juveniles and adults, as well as about shape sexual dimorphism.
Multi-material braids for multifunctional laminates: conductive through-thickness reinforcement
Authors: O’Keeffe Caroline , Pickard Laura Rhian , Cao Juan , Allegri Giuliano , Partridge Ivana K. , Ivanov Dmitry S. 
Published: February 2021

AbstractConventional carbon fibre laminates are known to be moderately electrically conductive in-plane, but have a poor through-thickness conductivity. This poses a problem for functionality aspects that are of increasing importance to industry, such as sensing, current collection, inductive/resistive heating, electromagnetic interference (EMI) shielding, etc. This restriction is of course more pronounced for non-conductive composite reinforcements such as glass, organic or natural fibres. Among various solutions to boost through-thickness electrical conductivity, tufting with hybrid micro-braided metal-carbon fibre yarns is one of the most promising. As a well-characterised method of through thickness reinforcement, tufting is easily implementable in a manufacturing environment. The hybridisation of materials in the braid promotes the resilience and integrity of yarns, while integrating metal wires opens up a wide range of multifunctional applications. Many configurations can be produced by varying braid patterns and the constituting yarns/wires. A predictive design tool is therefore necessary to select the right material configuration for the desired functional and structural performance. This paper suggests a fast and robust method for generating finite-element models of the braids, validates the prediction of micro-architecture and electrical conductivity, and demonstrates successful manufacturing of composites enhanced with braided tufts.