bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activated Endolysosomal Cation Channel TRPML1 Facilitates Maturation of α-Synuclein-Containing Autophagosomes
Authors: Pollmanns Maike R. , Beer Judith , Rosignol Ines , Rodriguez-Muela Natalia , Falkenburger Björn H. , Dinter Elisabeth 
Published: July 2022

Background: Protein aggregates are degraded via the autophagy-lysosome pathway and alterations in the lysosomal system leading to the accumulation of pathogenic proteins, including aggregates of α-synuclein in Parkinson’s disease (PD). The importance of the endolysosomal transient receptor potential cation channel, mucolipin subfamily 1 (TRPML1) for the lysosomal function is highlighted by the fact that TRPML1 mutations cause the lysosomal storage disease mucolipidosis type IV. In this study, we investigated the mechanism by which activation of TRPML1 affects the degradation of α-synuclein.Methods: As a model of α-synuclein pathology, we expressed the pathogenic A53Tα-synuclein mutant in HEK293T cells. These cells were treated with the synthetic TRPML1 agonist ML-SA1. The amount of α-synuclein protein was determined by immunoblots. The abundance of aggregates and autolysosomal vesicles was determined by fluorescence microscopy and immunocytochemistry. Findings were confirmed by life-cell imaging and by application of ML-SA1 and the TRPML1 antagonist ML-SI3 to human dopaminergic neurons and human stem cell-derived neurons.Results: ML-SA1 reduced the percentage of HEK293T cells with α-synuclein aggregates and the amount of α-synuclein protein. The effect of ML-SA1 was blocked by pharmacological and genetic inhibition of autophagy. Consistent with TRPML function, it required the membrane lipid PI(3,5)P2, and cytosolic calcium. ML-SA1 shifted the composition of autophagosomes towards a higher fraction of mature autolysosomes, also in presence of α-synuclein. In neurons, inhibition of TRPML1 by its antagonist ML-SI3 blocked autophagosomal clearance, whereas the agonist ML-SA1 shifted the composition of a-synuclein particles towards a higher fraction of acidified particles. ML-SA1 was able to override the effect of Bafilomycin A1, which blocks the fusion of the autophagosome and lysosome and its acidification.Conclusion: These findings suggest, that activating TRPML1 with ML-SA1 facilitates clearance of α-synuclein aggregates primarily by affecting the late steps of the autophagy, i.e., by promoting autophagosome maturation. In agreement with recent work by others, our findings indicate that TRPML1 might constitute a plausible therapeutic target for PD, that warrants further validation in rodent models of α-synuclein pathology.
Effect of a Low-Carbohydrate Diet With or Without Exercise on Anxiety and Eating Behavior and Associated Changes in Cardiometabolic Health in Overweight Young Women
Authors: Hu Mingzhu , Shi Qingde , Sun Shengyan , Hong Hin Ieong , Zhang Haifeng , Qi Fengxue , Zou Liye , Nie Jinlei 
Published: July 2022

BackgroundThe effectiveness of low-carbohydrate diets (LCDs) on weight loss and exercise for improving cardiometabolic fitness have been well documented in the literature, but the effects of LCDs and whether adding exercise to a LCD regime could additionally benefit mental health (e. g., by lowering the level of anxiety) and associated changes in eating behavior are less clear in overweight and obese populations. Therefore, this study aimed to investigate the effects of a 4-week LCD with or without exercise on anxiety and eating behavior, and to explore the associations between changes in the psychological state and physiological parameters (i.e., body composition, aerobic fitness, blood pressure, lipid profile, and metabolic hormones).MethodsSeventy-four overweight Chinese women [age: 20.8 ± 3.0 years, body mass index (BMI): 25.3 ± 3.3 kg·m−2] completed the 4-week randomized controlled trial, which included a LCD group (i.e., ~50 g daily carbohydrate intake) with exercise training 5 days/week (LC-EXE, n = 26), a LCD group without exercise training (LC-CON, n = 25) and a control group that did not modify their habitual diets and physical activity (CON, n = 23). Levels of anxiety, eating behavior scores and physiological parameters (i.e., body weight, V̇O2peak, blood pressure, fasting glucose, blood lipids, and serum metabolic hormones including insulin, C-peptide, leptin, and ghrelin) were measured before and after the intervention.ResultsThere were significant reductions in anxiety levels in the LC-EXE compared with the LC-CON group, while no statistical changes were found in eating behaviors in any conditions after the 4-week intervention. Significant reduction in weight (~3.0 kg or 4%, p &lt; 0.01) and decreases in insulin (~30% p &lt; 0.01), C-peptide (~20% p &lt; 0.01), and leptin (~40%, p &lt; 0.01) were found in both LC-CON and LC-EXE groups, but adding exercise to a LCD regime generated no additional effects. There were significant improvements in V̇O2peak (~15% p &lt; 0.01) and anxiety (~25% p &lt; 0.01) in the LC-EXE compared with the LC-CON group, while no statistical differences were found between CON and LC-CON treatments. Further analysis revealed a negative association (r = −0.32, p &lt; 0.01) between changes in levels of anxiety and changes in V̇O2peak in all participates, no other correlations were found between changes in psychological and physiological parameters.ConclusionAlthough the combination of a LCD and exercise may not induce additional reductions in body weight in overweight young females, exercise could be a useful add-on treatment along with a LCD to improve cardiometabolic health and lower anxiety levels.
Brazilian Reference Percentiles for Bioimpedance Phase Angle of Healthy Individuals
Authors: Mattiello Rita , Mundstock Eduardo , Ziegelmann Patrícia Klarmann 
Published: July 2022

ObjectivesThe present study was designed to estimate phase angle percentile curves for a broad age range of healthy individuals.MethodsThis is a cross-sectional study of healthy Brazilian individuals aged five to 80. InBodyS10 was used to assess phase angle. Reference curves were stratified by sex and estimated using Generalized additive models for location, scale, and shape as a continuous function of age. The phase angle determinants analyzed were physical activity, age, BMI, and SES variables.ResultsData were analyzed from 2,146 individuals, 1,189 (55.2%) of whom were female. In both sexes, the phase angles showed a similar pattern (an increasing trend from childhood to the teenage phase, followed by stabilization during adult ages and a decrease in old adults). In female, the relationship between phase angle and age were associated with BMI and family income. In the male, the relationship between phase angle and age were associated with skin color and family income.ConclusionsTo the best of our knowledge, it is the first attempt to apply the GAMLSS technique to estimate phase angle percentiles in a healthy population covering most of the life cycle. We also showed that there are different phase angle determinants according to sex.
Flavonoid Intake From Cocoa-Based Products and Adiposity Parameters in Adolescents in Spain
Authors: Laveriano-Santos Emily P. , Arancibia-Riveros Camila , Tresserra-Rimbau Anna , Castro-Barquero Sara , Ruiz-León Ana María , Estruch Ramón , Casas Rosa , Bodega Patricia , de Miguel Mercedes , de Cos-Gandoy Amaya , Martínez-Gómez Jesús , Rodríguez Carla , Santos-Beneit Gloria , Fernández-Alvira Juan M. , Fernández-Jiménez Rodrigo , Lamuela-Raventós Rosa M. 
Published: July 2022

BackgroundCocoa-based products are a good source of flavonoids, which may have beneficial effects on metabolic health.ObjectiveThe aim of this study is to assess the relationship between flavonoids from cocoa-based products and adiposity parameters in adolescents.MethodsA cross-sectional study was conducted involving 944 adolescents aged 11–14 years enrolled in the SI! Program for Secondary Schools trial in Spain with available baseline data from food frequency questionnaires and anthropometric measurements [weight, height, waist circumference (WC), and fat mass percentage (% FM) by bioimpedance analysis]. Fat mass index (FMI) and waist-to-height ratio (WHtR) were obtained by dividing fat mass by height and WC by height, respectively. Body mass index (BMI), WC, and FMI for age and gender z-score were calculated. Overweight/obesity was defined as BMI ≥ 85th percentile and excess adiposity as %FM or FMI ≥ 75th percentile. WC ≥ 90th percentile and WHtR with a 0.5 threshold were considered as criteria of abdominal obesity. Multilevel mixed-effect regressions were used to evaluate the association between flavonoids from cocoa-based products and adiposity parameters. Municipalities and schools were considered random effects.ResultsParticipants with a higher flavonoid intake from cocoa-based products had lower WC z-score [B = −0.04, 95% CI (−0.07; −0.01), P-for trend = 0.045] and WHtR [B = −0.01, 95% CI (−0.02; −0.01), P- for trend &lt; 0.001]. They also had lower probability of having abdominal obesity [OR 0.66, 95% CI (0.52; 0.85), P- for trend = 0.001]. Inverse associations were observed between flavonoids from cocoa powder and BMI z-score [B = −0.08, 95% CI (−0.12; −0.05), P &lt; 0.001], WC z-score [B = −0.06, 95% CI (−0.11; −0.02), P = 0.003], WHtR [B = −0.01, 95% CI (−0.01; −0.00), P &lt; 0.001], %FM [B = −1.11, 95% CI (−1.48; −0.75), P &lt; 0.001], and FMI z-score [B = −0.18, 95% CI (−0.20; −0.17), P &lt; 0.001]. Regarding dark chocolate, an inverse association only with WC z-score [B = −0.06, 95% CI (−0.08; −0.05), P &lt; 0.001] was found. However, no association was observed between flavonoids from milk chocolate intake and anthropometric parameters.ConclusionsA higher intake of flavonoids from cocoa-based products was associated with lower adiposity parameters and a lower probability of presenting abdominal obesity.
Dynamic Characteristics and Predictive Capability of Tumor Voxel Dose–Response Assessed Using 18F-FDG PET/CT Imaging Feedback
Authors: Chen Shupeng , Qin An , Yan Di 
Published: July 2022

PurposeTumor voxel dose–response matrix (DRM) can be quantified using feedback from serial FDG-PET/CT imaging acquired during radiotherapy. This study investigated the dynamic characteristics and the predictive capability of DRM.MethodsFDG-PET/CT images were acquired before and weekly during standard chemoradiotherapy with the treatment dose 2 Gy × 35 from 31 head and neck cancer patients. For each patient, deformable image registration was performed between the pretreatment/baseline PET/CT image and each weekly PET/CT image. Tumor voxel DRM was derived using linear regression on the logarithm of the weekly standard uptake value (SUV) ratios for each tumor voxel, such as SUV measured at a dose level normalized to the baseline SUV0. The dynamic characteristics were evaluated by comparing the DRMi estimated using a single feedback image acquired at the ith treatment week (i = 1, 2, 3, or 4) to the DRM estimated using the last feedback image for each patient. The predictive capability of the DRM estimated using 1 or 2 feedback images was evaluated using the receiver operating characteristic test with respect to the treatment outcome of tumor local–regional control or failure.ResultsThe mean ± SD of tumor voxel SUV measured at the pretreatment and the 1st, 2nd, 3rd, 4th, and last treatment weeks was 6.76 ± 3.69, 5.72 ± 3.43, 3.85 ± 2.22, 3.27 ± 2.25, 2.5 ± 1.79, and 2.23 ± 1.27, respectively. The deviations between the DRMi estimated using the single feedback image obtained at the ith week and the last feedback image were 0.86 ± 4.87, −0.06 ± 0.3, −0.09 ± 0.17, and −0.09 ± 0.12 for DRM1, DRM2, DRM3, and DRM4, respectively. The predictive capability of DRM3 and DRM4 was significant (p &lt; 0.001). The area under the curve (AUC) was increased with the increase in treatment dose level. The DRMs constructed using the single feedback image achieved an AUC of 0.86~1. The AUC was slightly improved to 0.94~1 for the DRMs estimated using 2 feedback images.ConclusionTumor voxel metabolic activity measured using FDG-PET/CT fluctuated noticeably during the first 2 treatment weeks and obtained a stabilized reduction rate thereafter. Tumor voxel DRM constructed using a single FDG-PET/CT feedback image after the 2nd treatment week (&gt;20 Gy) has a good predictive capability. The predictive capability improved continuously using a later feedback image and marginally improved when two feedback images were applied.
Development of a Mixed Hypnosis and Music Intervention Program for the Management of Pain, Anxiety, and Wellbeing in End-of-Life Palliative Care
Authors: Bissonnette Josiane , Pierre Stephica , Duong Anh Thu Julia , Pinard Anne-Marie , Rainville Pierre , Ogez David 
Published: July 2022

BackgroundThe palliative care people present needs that can be partially met by complementary intervention. Approaches based on the use of hypnosis and music are increasingly being studied and have shown potential benefits on pain, anxiety, and wellbeing for many populations including those in palliative care.ObjectiveThis study aims to present the initial process of creating and refining a hypnosis and music intervention program intended for persons in palliative care, with a panel of experts of diverse relevant backgrounds. It also aims to evaluate its feasibility, preliminary acceptability, and content.MethodsTo achieve the objectives, we followed ORBIT recommendations for the development and redesign of behavioral interventions (phase I a-b). Based on a meta-analysis, reference interventions were identified and then adapted to the target population. Twenty-two experts from different backgrounds were consulted to obtain their evaluation on the acceptability, feasibility, and content of the interventions.ResultThe various components of the program were deemed appropriate or very appropriate by over 80% of the experts. However, possible risks were raised related to some uncertainty about the reactions of individuals to the intervention. Several experts (32%) indicated potential adverse effects consisting of negative emotional experiences during the sessions. Modifications were proposed specifically to reduce or mitigate this risk. Over 90% of the experts considered that the revised program provides a safer and more appropriate intervention for palliative care persons.ConclusionA mixed intervention program with hypnosis and music has been developed and attained a high level of consensus by the experts. The proposed intervention is ready to be assessed for clinical efficacy in a pilot study (ORBIT Phase II).
A Study Protocol for the Management of Children With Juvenile Idiopathic Arthritis Based on ePROs
Authors: Shen Biyu , Shi Songsong , Cui Hengmei , Li Yunyun , Chen Haoyang , Jin Huan , Xu Jia , Liu Zuojia , Jin Yanliang 
Published: July 2022

BackgroundJuvenile idiopathic arthritis (JIA) is a common chronic rheumatic disease with no known cures, affecting children with the age of onset under 16 years. Patient-reported outcome (PRO) measures are an important basis for evaluating the impact of JIA and associated therapies, however, which is particular challenge in the pediatric setting. At present, no randomized controlled studies have investigated the effect and usability of ePROs symptom management for children with JIA.MethodsThis longitudinal, randomized, controlled trial will be carried out at outpatient and pediatric wards of the Shanghai Children's Medical Center affiliated to Shanghai Jiao Tong University School of Medicine. A total of one hundred children with JIA diagnosed according to the International League of Associations for Rheumatology (ILAR) patients are randomized to receive individualized symptom management based on ePROs or routine management. The primary outcome is the mean C-Ped-PROMIS T-scores of patients in the ePROs-based group and the control group. The secondary outcomes are the trajectories of C-Ped-PROMIS T-scores and HRQOL scores, and changing relationship between them. Data were collected at 5 time points: at enrollment (“baseline”) and at the time of follow-up visits scheduled at 1, 3, 6, and 12 months.DiscussionThe findings are expected to conclude that the symptom management based on ePROs for children with JIA can improve the symptom of JIA, and it is a feasible and effective way to monitor and intervene children with JIA.Clinical Trialhttp://www.chictr.org.cn/showproj.aspx?proj=132769; (ChiCTR2100050503)
Therapeutic vs. Suprapharmacological Metformin Concentrations: Different Effects on Energy Metabolism and Mitochondrial Function in Skeletal Muscle Cells in vitro
Authors: Pavlovic Kasja , Krako Jakovljevic Nina , Isakovic Andjelka M. , Ivanovic Tijana , Markovic Ivanka , Lalic Nebojsa M. 
Published: July 2022

Metformin is an oral antidiabetic agent that has been widely used in clinical practice for over 60 years, and is currently the most prescribed antidiabetic drug worldwide. However, the molecular mechanisms of metformin action in different tissues are still not completely understood. Although metformin-induced inhibition of mitochondrial respiratory chain Complex I and activation of AMP-activated protein kinase have been observed in many studies, published data is inconsistent. Furthermore, metformin concentrations used for in vitro studies and their pharmacological relevance are a common point of debate. The aim of this study was to explore the effects of different metformin concentrations on energy metabolism and activity of relevant signaling pathways in C2C12 muscle cells in vitro. In order to determine if therapeutic metformin concentrations have an effect on skeletal muscle cells, we used micromolar metformin concentrations (50 µM), and compared the effects with those of higher, millimolar concentrations (5 mM), that have already been established to affect mitochondrial function and AMPK activity. We conducted all experiments in conditions of high (25 mM) and low glucose (5.5 mM) concentration, in order to discern the role of glucose availability on metformin action. According to our results, micromolar metformin treatment did not cause Complex I inhibition nor AMPK activation. Also, cells cultured in low glucose medium were more sensitive to Complex I inhibition, mitochondrial membrane depolarization and AMPK activation by millimolar metformin, but cells cultured in high glucose medium were more prone to induction of ROS production. In conclusion, even though suprapharmacological metformin concentrations cause Complex I inhibition and AMPK activation in skeletal muscle cells in vitro, therapeutic concentrations cause no such effect. This raises the question if these mechanisms are relevant for therapeutic effects of metformin in skeletal muscle.
Numerical Computations of Entropy Generation and MHD Ferrofluid Filled in a Closed Wavy Configuration: Finite Element Based Study
Authors: Mahmood Rashid , Khan Y. , Rahman Nusrat , Majeed Afraz Hussain , Alameer A. , Faraz N. 
Published: July 2022

In this article, the thermal flow effects of inclined magnetohydrodynamics ferrofluid filled in a wavy cavity are studied by adopting the finite element method (FEM). The non-dimensional governing equations and model for different parameters are evaluated. The system of non-linear algebraic equations is computed by adopting the Newton method. A space involving quadratic polynomials (ℙ2) has been selected to compute for the velocity profile, while the pressure and temperature profiles are approximated by linear (ℙ1) finite element space of functions. The discrete systems of non-linear algebraic equations are computed by utilizing the Newton method. The vertical walls are considered cold, whereas the bottom wavy surface is considered hot and the top wavy surface is insulated. The effect of the pertinent parameters, like Ra=105, volume fraction (0.00≤ϕ≤0.06), inclination angle (0∘≤γ≤90∘), and amplitude of the wavy surface (0.02≤AR≤0.08) is investigated. Computational results are addressed as streamlines out, isotherms, and proper graphs for substantial amounts of interest. Increasing Hartmann number (Ha) leads to an increase in Bejan number (Be), while opposite behavior can be observed in the case of viscous, magnetic, and thermal irreversibility, that is, curves are decreased by increasing Ha. Under the influence of an inclined magnetic field, the mathematical structuring of the problem is manifested by continuity, momentum, and energy equations. These equations are solved by using the finite element method computation. The graphs of velocity and isotherm are compared to the relevant parameters. To predict the flow characteristics at different locations, cross-sectional lines representing the velocity field in the horizontal and vertical directions are also drawn. Magnetization’s impact on flow control, heat transfer, and various irreversibilities are also discussed. The Nuavg progressively declined with the enhancement in the amplitude of the wavy surface AR.
Design of a High-Speed OFDM-SAC-OCDMA-Based FSO System Using EDW Codes for Supporting 5G Data Services and Smart City Applications
Authors: Singh Mehtab , Kříž Jan , Kamruzzaman M. M. , Dhasarathan Vigneswaran , Sharma Abhishek , Abd El-Mottaleb Somia A. 
Published: July 2022

A novel free space optics (FSO) system is introduced in this article by combining orthogonal frequency division multiplexing (OFDM) with spectral amplitude coding optical code division multiple access (SAC-OCDMA) to be implemented in 5G technology and smart cities. Enhanced double-weight (EDW) codes are used as signature codes, while for the detection technique, single photodiode detection (SPD) is applied for the SAC-OCDMA system. OFDM with a four-quadrature amplitude modulation (4-QAM) scheme is assigned to the three users in the SAC-OCDMA system, each carrying 15 Gbps. Adverse weather conditions, such as clear, fog, haze, rain, and dust storm, that affect the FSO channel are considered. The performance of the proposed system is evaluated in terms of log of bit error rate and received power at different propagation distances. The simulation results show successful transmission of 3 × 15 Gbps with a propagation range of 3.45 km under clear air and 1.316, 1.045, and 0.7 km under rain conditions (light, medium, and heavy rain) with a received power of −12.6 dBm. As for haze conditions, the range and received power are 2.391 km with −13 dBm for low haze, 1.591 km with −12.7 dBm for medium haze, and 1.025 km with −12.6 dBm for heavy haze. The range is reduced and becomes 1.085, 0.784, and 0.645 km under fog conditions (light, medium, and heavy fog) with −12.6 dBm received power. Furthermore, the system achieved a range of 0.681, 0.232, and 0.102 km under dust conditions (light, medium, and heavy dust) with a received power of −16 dBm.