bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study
Authors: Olsen Thomas , Øvrebø Bente , Haj-Yasein Nadia , Lee Sindre , Svendsen Karianne , Hjorth Marit , Bastani Nasser E. , Norheim Frode , Drevon Christian A. , Refsum Helga , Vinknes Kathrine J. 
Published: March 2020

Abstract
Background
Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational potential in humans, we evaluated the effects of dietary methionine and cysteine restriction on cardiometabolic risk factors, plasma and urinary amino acid profile, serum fibroblast growth factor 21 (FGF21), and subcutaneous adipose tissue gene expression in women with overweight and obesity in a double-blind randomized controlled pilot study.

Methods
Twenty women with overweight or obesity were allocated to a diet low (Met/Cys-low, n = 7), medium (Met/Cys-medium, n = 7) or high (Met/Cys-high, n = 6) in methionine and cysteine for 7 days. The diets differed only by methionine and cysteine content. Blood and urine were collected at day 0, 1, 3 and 7 and subcutaneous adipose tissue biopsies were taken at day 0 and 7.

Results
Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys-low vs. Met/Cys-high group. The Met/Cys-low group had increased mRNA expression of lipogenic genes in adipose tissue including DGAT1. When we excluded one participant with high fasting insulin at baseline, the Met/Cys-low group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys-high group. The participants reported satisfactory compliance and that the diets were moderately easy to follow.

Conclusions
Our data suggest that dietary methionine and cysteine restriction may have beneficial effects on circulating biomarkers, including FGF21, and influence subcutaneous adipose tissue gene expression. These results will aid in the design and implementation of future large-scale dietary interventions with methionine and cysteine restriction.
Trial registration ClinicalTrials.gov Identifier: NCT03629392, registration date: 14/08/2018 https://clinicaltrials.gov/ct2/show/NCT03629392.
Life satisfaction and musculoskeletal complaints in a population seeking osteopathy care: consecutive sample of 611 patients
Authors: Vaughan Brett , Mulcahy Jane , Allen Thomas , Coupe Emi , Gobbo David , Nasser Leila , Pain Karen , Fitzgerald Kylie 
Published: March 2020

Abstract
Background
Life satisfaction is a component of the subjective well-being construct. Research consistently suggests that life satisfaction is associated with enhanced social benefits and improved health outcomes. However, its relationship to musculoskeletal health outcomes is underexplored. This study evaluates the life satisfaction of a patient population presenting with musculoskeletal complaints, and the relationship of life satisfaction with other health demographics and behaviours.

Method
The study used a consecutive sampling design. Patients attending the Victoria University Osteopathy Clinic (Melbourne, Australia) were invited to complete the PROMIS® General Life Satisfaction scale (GLSS) along with questions related to health demographics and behaviours.

Results
The GLSS T-score was not significantly different for gender, being born outside of Australia, speaking English at home, or complaint chronicity.

Conclusions
Life satisfaction did not appear to be related to a range of health and demographic variables in the current musculoskeletal pain cohort. The PROMIS® General Life Satisfaction scale could prove useful to explore the relationship between life satisfaction and treatment outcomes for musculoskeletal complaints.
CHOP: haplotype-aware path indexing in population graphs
Authors: Mokveld Tom , Linthorst Jasper , Al-Ars Zaid , Holstege Henne , Reinders Marcel 
Published: March 2020

AbstractThe practical use of graph-based reference genomes depends on the ability to align reads to them. Performing substring queries to paths through these graphs lies at the core of this task. The combination of increasing pattern length and encoded variations inevitably leads to a combinatorial explosion of the search space. Instead of heuristic filtering or pruning steps to reduce the complexity, we propose CHOP, a method that constrains the search space by exploiting haplotype information, bounding the search space to the number of haplotypes so that a combinatorial explosion is prevented. We show that CHOP can be applied to large and complex datasets, by applying it on a graph-based representation of the human genome encoding all 80 million variants reported by the 1000 Genomes Project.
Epigenetic predictors of all-cause mortality are associated with objective measures of neighborhood disadvantage in an urban population
Authors: Ward-Caviness Cavin K. , Pu Shirley , Martin Chantel L. , Galea Sandro , Uddin Monica , Wildman Derek E. , Koenen Karestan , Aiello Allison E. 
Published: March 2020

Abstract
Background
Neighborhood characteristics are robust predictors of overall health and mortality risk for residents. Though there has been some investigation of the role that molecular indicators may play in mediating neighborhood exposures, there has been little effort to incorporate newly developed epigenetic biomarkers into our understanding of neighborhood characteristics and health outcomes.

Methods
Using 157 participants of the Detroit Neighborhood Health Study with detailed assessments of neighborhood characteristics and genome-wide DNA methylation profiling via the Illumina 450K methylation array, we assessed the relationship between objective neighborhood characteristics and a validated DNA methylation-based epigenetic mortality risk score (eMRS). Associations were adjusted for age, race, sex, ever smoking, ever alcohol usage, education, years spent in neighborhood, and employment. A secondary model additionally adjusted for personal neighborhood perception. We summarized 19 neighborhood quality indicators assessed for participants into 9 principal components which explained over 90% of the variance in the data and served as metrics of objective neighborhood quality exposures.

Results
Of the nine principal components utilized for this study, one was strongly associated with the eMRS (β = 0.15; 95% confidence interval = 0.06–0.24; P = 0.002). This principal component (PC7) was most strongly driven by the presence of abandoned cars, poor streets, and non-art graffiti. Models including both PC7 and individual indicators of neighborhood perception indicated that only PC7 and not neighborhood perception impacted the eMRS. When stratified on neighborhood indicators of greenspace, we observed a potentially protective effect of large mature trees as this feature substantially attenuated the observed association.

Conclusion
Objective measures of neighborhood disadvantage are significantly associated with an epigenetic predictor of mortality risk, presenting a potential novel avenue by which neighborhood-level exposures may impact health. Associations were independent of an individual’s perception of their neighborhood and attenuated by neighborhood greenspace features. More work should be done to determine molecular risk factors associated with neighborhoods, and potentially protective neighborhood features against adverse molecular effects.
Comparative expression profiles of host circulating miRNAs in response to Trichinella spiralis infection
Authors: Ma Xiao Han , Ren Hui Jun , Peng Ruo Yu , Li Yi , Ming Liang 
Published: March 2020

AbstractTrichinellosis is an important food-borne parasitic zoonosis throughout the world. At present, the mechanisms of Trichinella spiralis infection remain unclear. Acquiring detailed information on the host-Trichinella interaction would be beneficial for the development of new strategies for trichinellosis control. Circulating miRNAs are stably detectable in the blood of humans and animals infected with parasites. Circulating miRNAs might regulate the expression of target genes in pathological responses during infection and might be novel potential biomarkers of parasitic diseases. In the present study, a total of ten differentially expressed circulating mouse miRNAs with |log2(fold change)| ≥ 1.0 and FDR < 0.01 were found during T. spiralis infection, of which five were upregulated and five were downregulated. GO and KEGG analyses showed that the target genes of the ten miRNAs were enriched in many signalling pathways, especially focal adhesion, MAPK pathway, and so on. The results of qRT-PCR showed that among the five upregulated miRNAs, mmu-miR-467a-3p and mmu-miR-467d-3p expression in mouse serum reached a peak at 30 days post-infection (dpi). The expression of mmu-miR-376b-3p and mmu-miR-664-3p increased significantly at 18 dpi and then decreased at 30 dpi. The expression of mmu-miR-292a-5p gradually decreased from 12 to 30 dpi. Among the 5 downregulated miRNAs, mmu-miR-199a-5p expression was significantly downregulated at 30 dpi, while the expression levels of the other four miRNAs (mmu-miR-455-5p, mmu-miR-125b-5p, mmu-miR-125a-5p, and mmu-miR-615-3p) were significantly lower compared with the control, showing a steady downregulation at different phases of infection. These findings will help to further understand the host-Trichinella interaction and provide promising serum biomarkers for trichinellosis.
Fixed point theorems for sum operator with parameter
Authors: Zhang Nan , Zhang Lingling , Zhou Bibo , Tian Huimin 
Published: March 2020

AbstractThis paper develops some new existence and uniqueness theorems of a fixed point for a class of sum operator equations with parameter$\lambda _{1}A(x,x)+\lambda _{2}B(x,x)+\lambda _{3}Cx+\lambda _{4}Dx=x$λ1A(x,x)+λ2B(x,x)+λ3Cx+λ4Dx=x, whereA,Bare two mixed monotone operators,Cis an increasing operator,Dis a decreasing operator. In the case of positive parameters, the results obtained in this paper extend many existing conclusions in the field of study. Furthermore, by using the properties of Green’s function and the above fixed point theorems of sum operator, the unique positive solution a class of fractional differential equations with integro-differential boundary value conditions is given. Application of the results to the study of fractional differential equations is also given in the article.
Monotonicity properties and bounds involving the two-parameter generalized Grötzsch ring function
Authors: Hai Guo-Jing , Zhao Tie-Hong 
Published: March 2020

AbstractIn the article, we present several new monotonicity properties and bounds involving the generalized Grötzsch ring functions $\mu _{a,b}$μa,b in the theory of Ramanujan’s generalized modular equation for $0< a, b<1$0<a,b<1. Our results are the variants and extensions of some previously known results.
Factors associated with cutaneous ulcers among children in two yaws-endemic districts in Ghana
Authors: Okine Rafiq Nii Attoh , Sarfo Bismark , Adanu Richard M. , Kwakye-Maclean Cynthia , Osei Francis Adjei 
Published: March 2020

Abstract
Background
Yaws is a chronic relapsing disease caused by Treponema pallidum subspecies pertunue, which can result in severe disability and deformities. Children below the age of 15 years in resource-poor communities are the most affected. Several non-specific factors facilitate the continuous transmission and resurgence of the disease. Endemic communities in rural Ghana continue to report cases despite the roll out of several intervention strategies in the past years. The objective of this study was to determine the factors associated with cutaneous ulcers among children in two yaws-endemic districts in Ghana.

Methods
A community-based unmatched 1:2 case-control study was conducted among children between 1 and 15 years. Data on socio-demographic, environmental and behavioral factors were collected using a structured questionnaire. Active case search and confirmation was done using the Dual Path Platform (DPP) Syphilis Screen and Confirm test kit. Data were analyzed using STATA 15. Logistic regression was done to determine the exposures that were associated with yaws infection at 0.05 significant level.

Results
Sixty-two cases and 124 controls were recruited for the study. The adjusted multivariable logistic regression model showed that yaws infection was more likely among individuals who reside in overcrowded compound houses (aOR = 25.42, 95% CI: 6.15–105.09) and with poor handwashing habits (aOR = 6.46, 95% CI: 1.89–22.04). Male (aOR = 4.15, 95% CI: 1.29–13.36) and increasing age (aOR = 5.90, 95% CI: 1.97–17.67) were also associated with yaws infection.

Conclusions
Poor personal hygiene, overcrowding and lack of access to improved sanitary facilities are the factors that facilitate the transmission of yaws in the Awutu Senya West and Upper West Akyem districts. Yaws was also more common among males and school-aged children. Improving living conditions, access to good sanitary facilities and encouraging good personal hygiene practices should be core features of eradication programs in endemic communities.
Refinement of a gravimetric geoid model for Japan using GOCE and an updated regional gravity field model
Authors: Matsuo Koji , Kuroishi Yuki 
Published: March 2020

AbstractWe developed a refined gravimetric geoid model for Japan on a 1 × 1.5 arc-minute (2 km) grid from a GOCE-based satellite-only global geopotential model and a regional gravity field model updated in this study. First, we have constructed a regional gravity field model for Japan using updated gravity datasets together with a residual terrain model: 323,431 land gravity data, 77,389 shipborne marine gravity data, and Sandwell’s v28.1 altimetry-derived global marine gravity model. Then, the geoid was determined with the gravity field model. The methodology for gravimetric geoid determination was based on the remove–compute–restore technique with Helmert’s second method of condensation of topography (Stokes–Helmert scheme). Here, the hybrid Meissl–Molodensky modified spheroidal Stokes kernel was employed to minimize the truncation error under an appropriate combination of different kinds of gravity data. In addition, a high-resolution GSI-DEM on a 0.4 × 0.4 arc-second (10 m) grid, together with the SRTM-DEM on a 7.5 × 11.25 arc-second (250 m) grid, was utilized for precisely applying terrain correction to the regional gravity field model. Consequently, we created a gravimetric geoid model for Japan, consistent with 971 GNSS/leveling geoid heights distributed over the four main islands of Japan with a standard deviation of 5.7 cm, showing a considerable improvement by 2.3 cm over the previous model (JGEOID2008). However, there remain some areas with large discrepancies between the computed and GNSS/leveling geoid heights in northern Japan (Hokkaido), mountainous areas in central Japan, and some coastal regions. Since terrestrial gravity data are especially sparse in these areas, we speculated that the largeness of the geoid discrepancies there could be partly attributed to the insufficient coverage and accuracy of gravity data. The Geospatial Information Authority of Japan has started airborne gravity surveys to be covered over the Japanese Islands, and in future, we plan to develop a geoid model for Japan further accurately by incorporating airborne gravity data to come.
Genotyping of a gene cluster for production of colibactin and in vitro genotoxicity analysis of Escherichia coli strains obtained from the Japan Collection of Microorganisms
Authors: Kawanishi Masanobu , Shimohara Chiaki , Oda Yoshimitsu , Hisatomi Yuuta , Tsunematsu Yuta , Sato Michio , Hirayama Yuichiro , Miyoshi Noriyuki , Iwashita Yuji , Yoshikawa Yuko , Sugimura Haruhiko , Mutoh Michihiro , Ishikawa Hideki , Wakabayashi Keiji , Yagi Takashi , Watanabe Kenji 
Published: March 2020

Abstract
Introduction
Colibactin is a small genotoxic molecule produced by enteric bacteria, including certain Escherichia coli (E. coli) strains harbored in the human large intestine. This polyketide-peptide genotoxin is considered to contribute to the development of colorectal cancer. The colibactin-producing (clb+) microorganisms possess a 54-kilobase genomic island (clb gene cluster). In the present study, to assess the distribution of the clb gene cluster, genotyping analysis was carried out among E. coli strains randomly chosen from the Japan Collection of Microorganisms, RIKEN BRC, Japan.

Findings
The analysis revealed that two of six strains possessed a clb gene cluster. These clb+ strains JCM5263 and JCM5491 induced genotoxicity in in vitro micronucleus (MN) tests using rodent CHO AA8 cells. Since the induction level of MN by JCM5263 was high, a bacterial umu test was carried out with a cell extract of the strain, revealing that the extract had SOS-inducing potency in the umu tester bacterium.

Conclusion
These results support the observations that the clb gene cluster is widely distributed in nature and clb+E. coli having genotoxic potencies is not rare among microorganisms.
Nonstandard theta Milstein method for solving stochastic multi-strain tuberculosis model
Authors: Sweilam Nasser H. , AL-Mekhlafi Seham M. 
Published: March 2020

AbstractIn this article, a novel stochastic multi-strain tuberculosis model is presented. Numerical simulations for this model are the main aim of this work. A non-standard theta Milstein method is constructed to study the proposed model, where the proposed method is based on choosing the weight factor theta. The main advantage of this method is it can be explicit or implicit with large stability regions using the idea of the weighed step introduced by R.E. Mickens. Mean-square stability of nonstandard theta Milstein method is studied. The new scheme shows a greater behavior compared to the theta Milstein method. It is concluded that the proposed scheme preserves the positivity of the solution and numerical stability in larger region than the standard method.
Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer
Authors: Lin Steven H. , Hobbs Brian P. , Verma Vivek , Tidwell Rebecca S. , Smith Grace L. , Lei Xiudong , Corsini Erin M. , Mok Isabel , Wei Xiong , Yao Luyang , Wang Xin , Komaki Ritsuko U. , Chang Joe Y. , Chun Stephen G. , Jeter Melenda D. , Swisher Stephen G. , Ajani Jaffer A. , Blum-Murphy Mariela , Vaporciyan Ara A. , Mehran Reza J. , Koong Albert C. , Gandhi Saumil J. , Hofstetter Wayne L. , Hong Theodore S. , Delaney Thomas F. , Liao Zhongxing , Mohan Radhe 
Published: March 2020

PURPOSE Whether dosimetric advantages of proton beam therapy (PBT) translate to improved clinical outcomes compared with intensity-modulated radiation therapy (IMRT) remains unclear. This randomized trial compared total toxicity burden (TTB) and progression-free survival (PFS) between these modalities for esophageal cancer. METHODS This phase IIB trial randomly assigned patients to PBT or IMRT (50.4 Gy), stratified for histology, resectability, induction chemotherapy, and stage. The prespecified coprimary end points were TTB and PFS. TTB, a composite score of 11 distinct adverse events (AEs), including common toxicities as well as postoperative complications (POCs) in operated patients, quantified the extent of AE severity experienced over the duration of 1 year following treatment. The trial was conducted using Bayesian group sequential design with three planned interim analyses at 33%, 50%, and 67% of expected accrual (adjusted for follow-up). RESULTS This trial (commenced April 2012) was approved for closure and analysis upon activation of NRG-GI006 in March 2019, which occurred immediately prior to the planned 67% interim analysis. Altogether, 145 patients were randomly assigned (72 IMRT, 73 PBT), and 107 patients (61 IMRT, 46 PBT) were evaluable. Median follow-up was 44.1 months. Fifty-one patients (30 IMRT, 21 PBT) underwent esophagectomy; 80% of PBT was passive scattering. The posterior mean TTB was 2.3 times higher for IMRT (39.9; 95% highest posterior density interval, 26.2-54.9) than PBT (17.4; 10.5-25.0). The mean POC score was 7.6 times higher for IMRT (19.1; 7.3-32.3) versus PBT (2.5; 0.3-5.2). The posterior probability that mean TTB was lower for PBT compared with IMRT was 0.9989, which exceeded the trial’s stopping boundary of 0.9942 at the 67% interim analysis. The 3-year PFS rate (50.8% v 51.2%) and 3-year overall survival rates (44.5% v 44.5%) were similar. CONCLUSION For locally advanced esophageal cancer, PBT reduced the risk and severity of AEs compared with IMRT while maintaining similar PFS.
Phase II trial of the CDK4 inhibitor PD0332991 in CDK4-amplified liposarcoma.
Authors: Dickson Mark Andrew , Keohan Mary Louise , Tap William D. , Antonescu Cristina , Landa Jonathan , Qin Li-Xuan , Dohrenwend Eric Gerard , Rathbone Dustin , Ustoyev Yelena , Condy Mercedes M , Singer Samuel , Schwartz Gary K. 
Published: March 2020

10002 Background: CDK4 is amplified in approximately 90% of well-differentiated/de-differentiated liposarcomas (WD/DDLS). The selective CDK4/CDK6 inhibitor PD0332991 (PD) inhibits growth and induces senescence in liposarcoma cell lines and xenografts. In a phase I trial of PD, several patients with progressive WD/DDLS had prolonged stable disease for several years. To determine the safety and efficacy of PD, a phase II study was performed. Methods: Participants were patients with advanced WD/DDLS. Eligibility criteria were age≥18 years, measurable WD/DDLS (RECIST 1.1), documented progression on at least one systemic therapy directly before enrollment, CDK4 amplification by fluorescence in situ hybridization and retinoblastoma protein (RB) expression by immunohistochemistry (≥1+). Pts received oral PD 200mg daily for 14 consecutive days in 21-day cycles. The primary endpoint was progression-free survival (PFS) at 12 weeks. Based on historical data, a promising result was defined as a 12-week PFS of ≥40% and not promising as ≤20%. The sample size was up to 28 evaluable patients. If 9 patients were progression free at 12 weeks, then PD would be considered to have activity in WD/DDLS. Results: Of 44 patients screened (42/44 CDK4 amplified; 41/44 RB+), 29 were enrolled and 27 were evaluable for the primary endpoint. Median age was 65 (range 37-83); 52% were male; ECOG scores were 0 (69%) or 1 (31%), and the median number of prior regimens was 1 (range 1-5). PFS at 12 weeks was 70% (19/27 patients; 90% CI 56-100%), and thus the study significantly exceeded its primary endpoint. At the data cutoff, the median PFS was 18 weeks. Seven patients remain on study with stable disease at 18-48 weeks of followup. Grade 3 and 4 events included anemia (grade 3, 14%), thrombocytopenia (grade 3, 17%; grade 4, 14%), neutropenia (grade 3, 41%; grade 4, 7%) and febrile neutropenia (3%). Dose reductions were required in 24% of patients. Conclusions: Among patients with WD/DDLS with CDK4 amplification and RB expression who had actively progressing disease despite prior systemic therapy, treatment with the CDK4 inhibitor PD0332991 was associated with improved PFS. A randomized phase 3 trial is planned.