bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whey protein sweetened with Stevia rebaudiana Bertoni (Bert.) increases mitochondrial biogenesis markers in the skeletal muscle of resistance-trained rats
Authors: Lima Yago Carvalho , Kurauti Mirian Ayumi , da Fonseca Alves Gabriel , Ferezini Jonathan , Piovan Silvano , Malta Ananda , de Almeida Fernanda Losi Alves , Gomes Rodrigo Mello , de Freitas Mathias Paulo Cezar , Milani Paula Gimenez , da Costa Silvio Cláudio , Mareze-Costa Cecilia Edna 
Published: September 2019

AbstractBackgroundA combination of resistance training and whey protein supplementation is a common practice among athletes and recreational exercisers to enhance muscle growth and strength. Although their safety as food additives is controversial, artificial sweeteners are present in whey protein supplements. Thus, natural sweeteners extracted from the leaves ofStevia rebaudianaare a potential alternative, due to their safety and health benefits. Here, we investigated the effects of whey protein sweetened withS. rebaudianaon physical performance and mitochondrial biogenesis markers in the skeletal muscle of resistance-trained rats.MethodsForty male Wistar rats were distributed into four groups: sedentary rats, trained rats, trained rats receiving whey protein and trained rats receiving whey protein sweetened withS. rebaudianaleaf extracts. Resistance training was performed by climbing a ladder 5 days per week, during 8-weeks. The training sessions consisted of four climbs carrying a load of 50, 75, 90, and 100% of the maximum load-carrying capacity which we determined before by performing a maximum load-carrying test for each animal. After this period, we collected plasma and tissues samples to evaluate biochemical, histological and molecular (western blot) parameters in these rats.ResultsDietary supplementation with whey protein sweetened withS. rebaudianasignificantly enhanced the maximum load-carrying capacity of resistance-trained rats, compared with non-sweetened whey protein supplementation. This enhanced physical performance was accompanied by an increase in the weight of the gastrocnemius and soleus muscle pads. Although the muscle pad of the biceps brachii was not altered, we observed a significant increase in PGC-1α expression, which was followed by a similar pattern in TFAM protein expression, two important mitochondrial biogenesis markers. In addition, a higher level of AMPK phosphorylation was observed in these resistance-trained rats. Finally, supplementation with whey protein sweetened withS. rebaudianaalso induced a significant decrease in retroperitoneal adipocyte diameter and an increase in the weight of brown adipose tissue pads in resistance-trained rats.ConclusionThe addition ofStevia rebaudianaleaf extracts to whey protein appears to be a potential strategy for those who want to increase muscular mass and strength and also improve mitochondrial function. This strategy may be useful for both athletes and patients with metabolic disorders, such as obesity and type 2 diabetes.
Targeting T cell metabolism in the tumor microenvironment: an anti-cancer therapeutic strategy
Authors: Yin Zhongping , Bai Ling , Li Wei , Zeng Tanlun , Tian Huimin , Cui Jiuwei 
Published: September 2019

Abstract
T cells play important roles in anti-tumor immunity. Emerging evidence has revealed that distinct metabolic changes impact the activation and differentiation of T cells. Tailoring immune responses by manipulating cellular metabolic pathways and the identification of new targets may provide new options for cancer immunotherapy. In this review, we focus on recent advances in the metabolic reprogramming of different subtypes of T cells and T cell functions. We summarize how metabolic pathways accurately regulate T cell development, differentiation, and function in the tumor microenvironment. Because of the similar metabolism in activated T cells and tumor cells, we also describe the effect of the tumor microenvironment on T cell metabolism reprogramming, which may provide strategies for maximal anti-cancer effects and enhancing the immunity of T cells. Thus, studies of T lymphocyte metabolism can not only facilitate the basic research of immune metabolism, but also provide potential targets for drug development and new strategies for clinical treatment of cancer.
Sample size estimation for randomised controlled trials with repeated assessment of patient-reported outcomes: what correlation between baseline and follow-up outcomes should we assume?
Authors: Walters Stephen J. , Jacques Richard M. , dos Anjos Henriques-Cadby Inês Bonacho , Candlish Jane , Totton Nikki , Xian Mica Teo Shu 
Published: September 2019

Abstract

Background
Patient-reported outcome measures (PROMs) are now frequently used in randomised controlled trials (RCTs) as primary endpoints. RCTs are longitudinal, and many have a baseline (PRE) assessment of the outcome and one or more post-randomisation assessments of outcome (POST). With such pre-test post-test RCT designs there are several ways of estimating the sample size and analysing the outcome data: analysis of post-randomisation treatment means (POST); analysis of mean changes from pre- to post-randomisation (CHANGE); analysis of covariance (ANCOVA).
Sample size estimation using the CHANGE and ANCOVA methods requires specification of the correlation between the baseline and follow-up measurements. Other parameters in the sample size estimation method being unchanged, an assumed correlation of 0.70 (between baseline and follow-up outcomes) means that we can halve the required sample size at the study design stage if we used an ANCOVA method compared to a comparison of POST treatment means method. So what correlation (between baseline and follow-up outcomes) should be assumed and used in the sample size calculation? The aim of this paper is to estimate the correlations between baseline and follow-up PROMs in RCTs.

Methods
The Pearson correlation coefficients between the baseline and repeated PROM assessments from 20 RCTs (with 7173 participants at baseline) were calculated and summarised.

Results
The 20 reviewed RCTs had sample sizes, at baseline, ranging from 49 to 2659 participants. The time points for the post-randomisation follow-up assessments ranged from 7 days to 24 months; 464 correlations, between baseline and follow-up, were estimated; the mean correlation was 0.50 (median 0.51; standard deviation 0.15; range − 0.13 to 0.91).

Conclusions
There is a general consistency in the correlations between the repeated PROMs, with the majority being in the range of 0.4 to 0.6. The implications are that we can reduce the sample size in an RCT by 25% if we use an ANCOVA model, with a correlation of 0.50, for the design and analysis. There is a decline in correlation amongst more distant pairs of time points.
Tick mitochondrial genomes: structural characteristics and phylogenetic implications
Authors: Wang Tianhong , Zhang Shiqi , Pei Tingwei , Yu Zhijun , Liu Jingze 
Published: September 2019

AbstractTicks are obligate blood-sucking arachnid ectoparasites from the order Acarina, and many are notorious as vectors of a wide variety of zoonotic pathogens. However, the systematics of ticks in several genera is still controversial. The mitochondrial genome (mt-genome) has been widely used in arthropod phylogeny, molecular evolution and population genetics. With the development of sequencing technologies, an increasing number of tick mt-genomes have been sequenced and annotated. To date, 63 complete tick mt-genomes are available in the NCBI database, and these genomes have become an increasingly important genetic resource and source of molecular markers in phylogenetic studies of ticks in recent years. The present review summarizes all available complete mt-genomes of ticks in the NCBI database and analyses their characteristics, including structure, base composition and gene arrangement. Furthermore, a phylogenetic tree was constructed using mitochondrial protein-coding genes (PCGs) and ribosomal RNA (rRNA) genes from ticks. The results will provide important clues for deciphering new tick mt-genomes and establish a foundation for subsequent taxonomic research.
Spatial temporal graph convolutional networks for skeleton-based dynamic hand gesture recognition
Authors: Li Yong , He Zihang , Ye Xiang , He Zuguo , Han Kangrong 
Published: September 2019

AbstractHand gesture recognition methods play an important role in human-computer interaction. Among these methods are skeleton-based recognition techniques that seem to be promising. In literature, several methods have been proposed to recognize hand gestures with skeletons. One problem with these methods is that they consider little the connectivity between the joints of a skeleton, constructing simple graphs for skeleton connectivity. Observing this, we built a new model of hand skeletons by adding three types of edges in the graph to finely describe the linkage action of joints. Then, an end-to-end deep neural network, hand gesture graph convolutional network, is presented in which the convolution is conducted only on linked skeleton joints. Since the training dataset is relatively small, this work proposes expanding the coordinate dimensionality so as to let models learn more semantic features. Furthermore, relative coordinates are employed to help hand gesture graph convolutional network learn the feature representation independent of the random starting positions of actions. The proposed method is validated on two challenging datasets, and the experimental results show that it outperforms the state-of-the-art methods. Furthermore, it is relatively lightweight in practice for hand skeleton-based gesture recognition.
Numerical solution of stochastic state-dependent delay differential equations: convergence and stability
Authors: Akhtari Bahar 
Published: September 2019

Abstract
Numerical analysis of stochastic delay differential equations has been widely developed but frequently for the cases where the delay term has a simple feature. In this paper, we aim to study a more general case of delay term which has not been much discussed so far. We mean the case where the delay term takes random values. For this purpose, a new continuous split-step scheme is introduced to approximate the solution and then convergence in the mean-square sense is investigated. Moreover, given a test equation, the mean-square asymptotic stability of the scheme is presented. Numerical examples are provided to further illustrate the obtained theoretical results.
Retrieved lymph nodes from different anatomic groups in gastric cancer: a proposed optimal number, comparison with other nodal classification strategies and its impact on prognosis
Authors: Pan Siwei , Wang Pengliang , Xing Yanan , Li Kai , Wang Zhenning , Xu Huimian , Zhu Zhi 
Published: September 2019

AbstractBackgroundThe optimal number of retrieved lymph nodes (LNs) in gastric cancer (GC) is still debatable and previous studies proposing new classification alternatives mostly focused on the number of retrieved LNs without proper consideration on the anatomic nodal groups’ location. Here, we assessed the impact of retrieved LNs from different nodal location groups on the survival of GC patients.MethodsStage I–III gastric cancer patients who had radical gastrectomy were investigated. LN grouping was determined according to the 13th edition of the JCGC. The optimal cut‐off values of retrieved LNs in different LN groups (Group 1 and 2) were calculated, based on which a proposed nodal classification (rN) simultaneously accounting the optimal number and location of retrieved LNs was proposed. The performance of rN was then compared to that of LN ratio, log‐odds of metastatic LNs (LODDs) and the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) N classification.ResultsThe optimal cut‐off values for Group 1 and 2 were 13 and 9, respectively. The 5‐year overall survival (OS) was higher for patients in retrieved Group 1 LNs > 13 (vs. Group 1 LNs ≤ 13, 63.2% vs. 57.9%, P = 0.005) and retrieved Group 2 LNs > 9 (vs. Group 2 LNs ≤ 9, 72.5% vs. 60.7%, P = 0.009). Patients staged as pN0–3b were sub classified using this Group 1 and 2 nodal analogy. The OS of pN0–N2 patients in retrieved Group 1 LNs > 13 or Group 2 LNs > 9 were superior to those in retrieved Group 1 LNs ≤ 13 and Group 2 LNs ≤ 9 (All P < 0.05); except for pN3 patients. The rN classification was formulated and demonstrated better 5‐year OS prognostication performance as compared to the LNR, LODDs, and the 8th UICC/AJCC N staging system.ConclusionsThe retrieval of > 13 and > 9 LNs for Group 1 and Group 2, respectively, could represent an alternative lymph node retrieval approach in radical gastrectomy for more precise survival prognostication and minimizing staging migration, especially if > 16 LNs is found to be difficult.
Comprehensive framework between environment and genomic stability: the open symposium of the Japanese Environmental Mutagen Society (JEMS) in 2019
Authors: Horibata Katsuyoshi , Sekimoto Masashi , Sugiyama Kei-ichi 
Published: September 2019

Abstract
The open symposium of the Japanese Environmental Mutagen Society (JEMS), under the title of “Comprehensive framework between environment and genomic stability,” was held in the Main Conference Room of the Foundation for Promotion of Cancer Research, Tokyo, on June 8, 2019. To understand the relationship between genes and environmental mutagens, the symposium highlights the research activities in the fields of cancer, carcinogenesis and related diseases caused by genomic instabilities, including epigenetic and metabolomic alterations. The symposium was planned to help familiarize attendees with the current trends in research on genome safety. The organizers herein present a summary of the symposium.
Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial
Authors: Kim Hyun-Ah , Lee Jong Won , Nam Seok Jin , Park Byeong-Woo , Im Seock-Ah , Lee Eun Sook , Jung Yong Sik , Yoon Jung Han , Kang Sung Soo , Lee Soo-Jung , Park Kyong Hwa , Jeong Joon , Cho Se-Heon , Kim Sung Yong , Kim Lee Su , Moon Byung-In , Lee Min Hyuk , Kim Tae Hyun , Park Chanheun , Jung Sung Hoo , Gwak Geumhee , Kim Jeryong , Kang Sun Hee , Jin Young Woo , Kim Hee Jeong , Han Se-Hwan , Han Wonshik , Hur Min Hee , Noh Woo Chul ,   on behalf of the Korean Breast Cancer Study Group
Published: September 2019

PURPOSE The addition of ovarian function suppression (OFS) for 5 years to tamoxifen (TAM) for treatment of premenopausal patients with breast cancer after completion of chemotherapy has beneficial effects on disease-free survival (DFS). This study evaluated the efficacy of adding 2 years of OFS to TAM in patients with hormone receptor–positive breast cancer who remain in a premenopausal state or resume ovarian function after chemotherapy. PATIENTS AND METHODS We enrolled 1,483 premenopausal women (age ≤ 45 years) with estrogen receptor–positive breast cancer treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy. Ovarian function was assessed every 6 months for 2 years since enrollment on the basis of follicular-stimulating hormone levels and vaginal bleeding history. If ovarian function was confirmed to be premenopausal at each visit, the patient was randomly assigned to complete 5 years of TAM alone (TAM-only) group or 5 years of TAM with OFS for 2 years that involved monthly goserelin administration (TAM + OFS) group. DFS was defined from the time of enrollment to the time of the first event. RESULTS A total of 1,293 patients were randomly assigned, and 1,282 patients were eligible for analysis. The estimated 5-year DFS rate was 91.1% in the TAM + OFS group and 87.5% in the TAM-only group (hazard ratio, 0.69; 95% CI, 0.48 to 0.97; P = .033). The estimated 5-year overall survival rate was 99.4% in the TAM + OFS group and 97.8% in the TAM-only group (hazard ratio, 0.31; 95% CI, 0.10 to 0.94; P = .029). CONCLUSION The addition of 2 years of OFS to TAM significantly improved DFS compared with TAM alone in patients who remained premenopausal or resumed ovarian function after chemotherapy.
Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial
Authors: Matulonis Ursula A. , Walder Lydia , Nøttrup Trine J. , Bessette Paul , Mahner Sven , Gil-Martin Marta , Kalbacher Elsa , Ledermann Jonathan A. , Wenham Robert M. , Woie Kathrine , Lau Susie , Marmé Frederik , Casado Herraez Antonio , Hardy-Bessard Anne-Claire , Banerjee Susana , Lindahl Gabriel , Benigno Benedict , Buscema Joseph , Travers Karin , Guy Holly , Mirza Mansoor R. 
Published: September 2019

PURPOSE This study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer. PATIENTS AND METHODS Mean progression-free survival (PFS) was estimated for niraparib and RS by fitting parametric survival distributions to Kaplan-Meier data for 553 patients with recurrent ovarian cancer who were enrolled in the phase III ENGOT-OV16/NOVA trial. Patients were categorized according to the presence or absence of a germline BRCA mutation—g BRCAmut and non-g BRCAmut cohorts. Mean time with toxicity was estimated based on the area under the Kaplan-Meier curve for symptomatic grade 2 or greater fatigue, nausea, and vomiting adverse events (AEs). Time with toxicity was the number of days a patient experienced an AE post–random assignment and before disease progression. TWiST was estimated as the difference between mean PFS and time with toxicity. Uncertainty was explored using alternative PFS estimates and considering all symptomatic grade 2 or greater AEs. RESULTS In the g BRCAmut and non-g BRCAmut cohorts, niraparib treatment resulted in a mean PFS benefit of 3.23 years and 1.44 years, respectively, and a mean time with toxicity of 0.28 years and 0.10 years, respectively, compared with RS. Hence, niraparib treatment resulted in a mean TWiST benefit of 2.95 years and 1.34 years, respectively, compared with RS, which is equivalent to more than four-fold and two-fold increases in mean TWiST between niraparib and RS in the g BRCAmut and non-g BRCAmut cohorts, respectively. This TWiST benefit was consistent across all sensitivity analyses, including modeling PFS over 5-, 10-, and 15-year time horizons. CONCLUSION Patients who were treated with niraparib compared with RS experienced increased mean TWiST. Thus, patients who were treated with niraparib in the ENGOT-OV16/NOVA trial experienced more time without symptoms or symptomatic toxicities compared with control.
Guiding Opioid Administration by 3 Different Analgesia Nociception Monitoring Indices During General Anesthesia Alters Intraoperative Sufentanil Consumption and Stress Hormone Release: A Randomized Controlled Pilot Study
Authors: Funcke Sandra , Pinnschmidt Hans O. , Wesseler Stefan , Brinkmann Charlotte , Beyer Burkhard , Jazbutyte Virginija , Behem Christoph R. , Trepte Constantin , Nitzschke Rainer 
Published: September 2019

BACKGROUND:
This pilot study investigated the effect of sufentanil titration by 3 different analgesia monitoring devices or clinical signs during general anesthesia.

METHODS:
Forty-eight patients undergoing radical retropubic prostatectomy with sevoflurane/sufentanil anesthesia were randomly assigned into 4 groups and received sufentanil guided either by 1 of 3 analgesia monitoring devices (Surgical Pleth Index [SPI], Pupillary Pain Index [PPI], Nociception Level [NoL]) or by clinical judgment (control). The primary end point was intraoperative sufentanil consumption. Adrenocorticotropic hormone (ACTH) and cortisol were measured at 4 time points during the day of surgery. Data were analyzed by Kruskal–Wallis and Mann–Whitney U tests and by mixed model and area under the curve (AUC) analyses for group comparisons and time effects of stress hormones.

RESULTS:
The total amount of sufentanil administration (μg·kg−1·minute−1·10−3) differed between the groups (median [quartiles]: control = 5.6 [4.4–6.4], SPI = 7.2 [4.8–8.4], PPI = 2.0 [1.8–2.9], NoL = 3.8 [3.3–5.1]; PPI versus SPI, −5.1 [−6.6 to −1.3], P < .001; NoL versus SPI, −3.0 [−5.2 to 0.2], P = .024; control versus SPI, −1.6 [−3.7 to 1.7], P = .128; NoL versus PPI, 1.7 [0.6–3.4], P < .001; control versus PPI, 3.4 [2.0–4.6], P < .001; control versus NoL, 1.6 [−0.2 to 3.3], P = .017) (Hodges–Lehmann estimator [99% confidence interval {CI}], P values). The AUC analysis indicated differences among groups in cumulative ACTH levels (ng·liter−1·minute, natural logarithm (ln)-transformed data) of NoL versus PPI (−1.079 [−1.950 to −0.208], P = .001) and PPI versus SPI (1.192 [0.317–2.068], P= .001), as well as differences in cortisol levels (µg·liter−1·minute) for PPI versus SPI (46,710 [21,145–72,274], P < .001), NoL versus SPI (27,645 [3163–52,126], P = .003), and control versus SPI (31,824 [6974–56,675], P = .001) (differences in means [99% CI], P value). Secondary end points (postoperative recovery, pain level, and analgesia medication) showed no differences.

CONCLUSIONS:
The type of analgesia nociception monitoring affected the total amount of sufentanil administered. Lower sufentanil doses in the PPI group were associated with an increased endocrine stress response. Titration by SPI caused no opioid reduction compared to the control but was associated with a reduced endocrine stress response.
mTOR hyperactivity mediates lysosomal dysfunction in Gaucher's disease iPSC-neuronal cells
Authors: Brown Robert A. , Voit Antanina , Srikanth Manasa P. , Thayer Julia A. , Kingsbury Tami J. , Jacobson Marlene A. , Lipinski Marta M. , Feldman Ricardo A. , Awad Ola 
Published: September 2019

ABSTRACT
Bi-allelic GBA1 mutations cause Gaucher's disease (GD), the most common lysosomal storage disorder. Neuronopathic manifestations in GD include neurodegeneration, which can be severe and rapidly progressive. GBA1 mutations are also the most frequent genetic risk factors for Parkinson's disease. Dysfunction of the autophagy-lysosomal pathway represents a key pathogenic event in GBA1-associated neurodegeneration. Using an induced pluripotent stem cell (iPSC) model of GD, we previously demonstrated that lysosomal alterations in GD neurons are linked to dysfunction of the transcription factor EB (TFEB). TFEB controls the coordinated expression of autophagy and lysosomal genes and is negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1). To further investigate the mechanism of autophagy-lysosomal pathway dysfunction in neuronopathic GD, we examined mTORC1 kinase activity in GD iPSC neuronal progenitors and differentiated neurons. We found that mTORC1 is hyperactive in GD cells as evidenced by increased phosphorylation of its downstream protein substrates. We also found that pharmacological inhibition of glucosylceramide synthase enzyme reversed mTORC1 hyperactivation, suggesting that increased mTORC1 activity is mediated by the abnormal accumulation of glycosphingolipids in the mutant cells. Treatment with the mTOR inhibitor Torin1 upregulated lysosomal biogenesis and enhanced autophagic clearance in GD neurons, confirming that lysosomal dysfunction is mediated by mTOR hyperactivation. Further analysis demonstrated that increased TFEB phosphorylation by mTORC1 results in decreased TFEB stability in GD cells. Our study uncovers a new mechanism contributing to autophagy-lysosomal pathway dysfunction in GD, and identifies the mTOR complex as a potential therapeutic target for treatment of GBA1-associated neurodegeneration.