bluuebunny/crossref_metadata_2025_split huggingface dataset:
LTBP1 promotes esophageal squamous cell carcinoma progression through epithelial-mesenchymal transition and cancer-associated fibroblasts transformation
Authors: Cai Rui , Wang Ping , Zhao Xin , Lu Xiansheng , Deng Ruxia , Wang Xiaoyu , Su Zhaoji , Hong Chang , Lin Jie 
Published: March 2020

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide. Due to its high morbidity and mortality rates, it is urgent to find a molecular target that contributes to esophageal carcinogenesis and progression. In this research, we aimed to investigate the functions of Latent transforming growth factor β binding protein 1(LTBP1) in ESCC progression and elucidate the underlying mechanisms.

Methods
The tandem mass tag-based quantitative proteomic approach was applied to screen the differentially expressed proteins (DEPs) between 3 cases of ESCC tumor samples and paired normal tissues. Then the DEPs were validated in human ESCC tissues using western blot assays and GEPIA database respectively. The expression level of LTBP1 was detected in 152 cases of ESCC tissues and paired normal tissues. Loss-of-function assays were performed to detect the function of LTBP1 in vivo and in vitro. Immunofluorescence and Western blot assays were used to detect the expression of apoptosis, epithelial–mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) markers.

Results
A total of 39 proteins were screened to be up-regulated (ratio > 2.0) in all three ESCC tissues. The results of immunohistochemistry assays indicated that the expression level of LTBP1 was higher in ESCC tissues than that in paired normal tissues (p < 0.001). Overexpression of LTBP1 was positively associated with lymphatic metastasis in ESCC (p = 0.002). Down-regulation of LTBP1 inhibited the invasion and migration as well as metastatic abilities in vitro and in vivo. It was also observed the down-regulation of LTBP1 not only decreased the mesenchymal phenotypes but also inhibited TGFβ-induced EMT in ESCC cells. We further found that down-regulation of LTBP1 enhanced ESCC cells’ sensitivity to 5-FU treatment. Inhibition of LTBP1 expression could also attenuate induction of CAFs transformation and restrain fibroblast express fibronectin (FN1) in ESCC cells.

Conclusion
Overexpression of LTBP1 was associated with lymph node metastasis in ESCC. Our results indicated that LTBP1 not only increased the malignant behaviors of ESCC cells but also induced EMT and CAFs transformation. Our studies suggested an oncogenic role of LTBP1 in ESCC progression and it may serve as a potential therapeutic target for ESCC patients.
RETRACTED ARTICLE: HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression
Authors: Song Huajie , Li Dan , Wang Xiaojing , Fang Erhu , Yang Feng , Hu Anpei , Wang Jianqun , Guo Yanhua , Liu Yang , Li Hongjun , Chen Yajun , Huang Kai , Zheng Liduan , Tong Qiangsong 
Published: March 2020

Abstract
Background
Aerobic glycolysis is a hallmark of metabolic reprogramming that contributes to tumor progression. However, the mechanisms regulating expression of glycolytic genes in neuroblastoma (NB), the most common extracranial solid tumor in childhood, still remain elusive.

Methods
Crucial transcriptional regulators and their downstream glycolytic genes were identified by integrative analysis of a publicly available expression profiling dataset. In vitro and in vivo assays were undertaken to explore the biological effects and underlying mechanisms of transcriptional regulators in NB cells. Survival analysis was performed by using Kaplan-Meier method and log-rank test.

Results
Hepatocyte nuclear factor 4 alpha (HNF4A) and its derived long noncoding RNA (HNF4A-AS1) promoted aerobic glycolysis and NB progression. Gain- and loss-of-function studies indicated that HNF4A and HNF4A-AS1 facilitated the glycolysis process, glucose uptake, lactate production, and ATP levels of NB cells. Mechanistically, transcription factor HNF4A increased the expression of hexokinase 2 (HK2) and solute carrier family 2 member 1 (SLC2A1), while HNF4A-AS1 bound to heterogeneous nuclear ribonucleoprotein U (hnRNPU) to facilitate its interaction with CCCTC-binding factor (CTCF), resulting in transactivation of CTCF and transcriptional alteration of HNF4A and other genes associated with tumor progression. Administration of a small peptide blocking HNF4A-AS1-hnRNPU interaction or lentivirus-mediated short hairpin RNA targeting HNF4A-AS1 significantly suppressed aerobic glycolysis, tumorigenesis, and aggressiveness of NB cells. In clinical NB cases, high expression of HNF4A-AS1, hnRNPU, CTCF, or HNF4A was associated with poor survival of patients.

Conclusions
These findings suggest that therapeutic targeting of HNF4A-AS1/hnRNPU/CTCF axis inhibits aerobic glycolysis and NB progression.
Prognostic impact of elevated lactate levels on mortality in critically ill patients with and without preadmission metformin treatment: a Danish registry-based cohort study
Authors: Posma Rene A. , Frøslev Trine , Jespersen Bente , van der Horst Iwan C. C. , Touw Daan J. , Thomsen Reimar W. , Nijsten Maarten W. , Christiansen Christian F. 
Published: March 2020

Abstract
Background
Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers.

Methods
This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model.

Results
Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users.

Conclusion
In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.
Depression, anxiety, stress, and dysmenorrhea: a protocol for a systematic review
Authors: Pakpour Amir H. , Kazemi Farideh , Alimoradi Zainab , Griffiths Mark D. 
Published: March 2020

Abstract
Background
Dysmenorrhea is one of the most common menstrual disorders and is influenced by various factors. Psychological disorders including anxiety, depression, and stress have been suggested as influencing dysmenorrhea, but previous findings are inconsistent. This study will investigate the relationship between depression/anxiety/stress and dysmenorrhea using a systematic review and meta-analysis.

Methods
Online databases including PsycINFO, Scopus, PubMed, Science Direct, ProQuest, ISI Web of Knowledge, and Embase will be searched. Appropriate keywords and MeSH terms will be used to retrieve the journal papers published from 1990 until the end of December 2019. To improve search coverage, the reference lists of all included studies will be reviewed to find eligible papers. Inclusion criteria include the following: descriptive, cohort, case-control, and cross-sectional studies; the relationship between depression/anxiety/stress and dysmenorrhea being an objective of the study; and published in peer-reviewed journals. The paper selection, data extraction, and quality assessment of selected studies will be performed independently by two researchers, and disagreements will be resolved through discussions. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the quality of selected studies. A quantitative synthesis will be performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) via the STATA software, if retrieving enough number of studies with no severe methodological heterogeneities. Otherwise, qualitative synthesis will be used to report the findings.

Discussion
To the best of our knowledge, this will be the first systematic review on this topic. Performing an inclusive search in major databases over a wide timescale is one key strength of the proposed study and will maximize the coverage of the original research studies on this topic. Results of present study are expected to lead to deeper understanding the relationship between common mental health conditions and dysmenorrhea.

Systematic review registration
PROSPERO CRD42018102199
Exploring coupled images fusion based on joint tensor decomposition
Authors: Lu Liangfu , Ren Xiaoxu , Yeh Kuo-Hui , Tan Zhiyuan , Chanussot Jocelyn 
Published: March 2020

Abstract
Data fusion has always been a hot research topic in human-centric computing and extended with the development of artificial intelligence. Generally, the coupled data fusion algorithm usually utilizes the information from one data set to improve the estimation accuracy and explain related latent variables of other coupled datasets. This paper proposes several kinds of coupled images decomposition algorithms based on the coupled matrix and tensor factorization-optimization (CMTF-OPT) algorithm and the flexible coupling algorithm, which are termed the coupled images factorization-optimization (CIF-OPT) algorithm and the modified flexible coupling algorithm respectively. The theory and experiments show that the effect of the CIF-OPT algorithm is robust under the influence of different noises. Particularly, the CIF-OPT algorithm can accurately restore an image with missing some data elements. Moreover, the flexible coupling model has better estimation performance than a hard coupling. For high-dimensional images, this paper adopts the compressed data decomposition algorithm that not only works better than uncoupled ALS algorithm as the image noise level increases, but saves time and cost compared to the uncompressed algorithm.
Public reporting on pharmaceutical industry-led access programs: alignment with the WHO medicine programs evaluation checklist
Authors: Umeh Chukwuemeka A. , Rockers Peter C. , Laing Richard , Wagh Ovi , Wirtz Veronika J. 
Published: March 2020

Abstract
Background
There has been increased demand for greater public accountability and transparency of private sector-led global health partnership programs. This study critically reviews and pilot tests the World Health Organization (WHO) medicine program checklist as a framework for public reporting and assessing of programs.

Methods
We reviewed each question on the WHO checklist for clarity and usability. Next, we pilot tested the subset of checklist questions focused on program assessment. We extracted and analyzed publicly available information on one randomly selected program from each of the 20 largest research-based biopharmaceutical companies. For each program, we assessed whether publicly available information allowed for an assessment of each relevant question in the checklist.

Results
Checklist questions fit in four main categories: [1] national health and development plans, needs, capacity, laws and policies; [2] financial, performance, and public accountability; [3] risk management and mitigation strategies; and [4] long-term sustainability. Nearly all (21 of 22) questions in the checklist require information best provided by companies; one question requires information best provided by governments.
Programs frequently reported on the public health needs of their programs (100%), program objectives and activities (100%) and the actual or expected program outputs (95%). There was less information on program alignment with country plans and capacity (50%), detailed program monitoring and evaluation plan (20%), risks mitigation strategies (5%), program needs assessment (5%), and additional resources required from or contributed by government (0%).

Conclusion
The WHO checklist of key considerations for evaluating proposals for access to medicine programs could be a useful framework for public reporting of program information as most of checklist questions ask for data that should be available to those leading the program. Further revisions of the WHO checklist will help refine it to improve clarity and content validity.
Demographic assessment of the Dalmatian dog – effective population size, linkage disequilibrium and inbreeding coefficients
Authors: Vasiliadis Danae , Metzger Julia , Distl Ottmar 
Published: March 2020

Abstract
Background
The calculation of demographic measures is a useful tool for evaluating the genomic architecture of dog breeds and enables ranking dog breeds in terms of genetic diversity. To achieve this for the German Dalmatian dog population, 307 purebred animals of this breed were genotyped on the Illumina Canine high density BeadChip. The analysis of pedigree-based inbreeding was performed based on a pedigree with 25,761 dogs including the genotyped dogs.

Results
The effective population size derived from squared correlation coefficients between SNP alleles (r2) was 69. The maximum value of r2 was 0.56, resulting in a 50% decay value of 0.28 at a marker distance of 37.5 kb. The effective population size calculated from pedigree data using individual increase in inbreeding over equivalent generations was 116. The pedigree inbreeding coefficient was 0.026. The genomic inbreeding coefficient based on the length of runs of homozygosity (ROH) was calculated for seven length categories of ROHs, and ranged from 0.08 to 0.28. The fixation coefficients FIS_PED and FIS_GENO were at 0.017 and 0.004. PANTHER statistical overrepresentation analysis of genes located in consensus ROHs revealed highly underrepresented biological processes in 50% of the investigated dogs. One of those is the 0.28 fold enriched “immune response”, which might be associated to the high prevalence of allergic dermatitis in the breed. Candidate genes for congenital sensorineural deafness (CCSD, a highly prevalent disease in the Dalmatian) were discovered in consensus ROHs.

Conclusions
The fast decay of r2 and the moderate inbreeding coefficients indicate that the German Dalmatian dog population is rather diverse. Pedigree- and genomic-based inbreeding measures were highly correlated and therefore prove good reliability for the given population. Analyses of consensus ROHs with genes coding for deafness and other breed-defining traits, such as hyperuricosuria, indicate that those ROH became fixed in the Dalmatian population about 500 years ago. In case of the Dalmatian dog, a ROH of 40 SNPs length is enough to investigate signatures of selection (e.g. the ROH with the fixed hyperuricosuria mutation) as far back as the breed formation point approximately 500 years ago.
A reporting checklist for HealthMeasures’ patient-reported outcomes: ASCQ-Me, Neuro-QoL, NIH Toolbox, and PROMIS
Authors:   on behalf of the HealthMeasures Team, Hanmer Janel , Jensen Roxanne E. , Rothrock Nan 
Published: March 2020

Abstract
Background
ASCQ-Me®, Neuro-QoL™, NIH Toolbox®, and PROMIS®, which are health-related quality of life measures collectively known as HealthMeasures, have experienced rapid uptake in the scientific community with over 1700 peer-reviewed publications through 2018. Because of their proliferation across multiple research disciplines, there has been significant heterogeneity in the description and reporting of these measures. Here, we provide a publication checklist to promote standardization and comparability across different reports. This checklist can be used across all HealthMeasures systems.
Checklist Development: Authors drafted a draft checklist, circulated among the HealthMeasures Steering Committee and PROMIS Health Organization until the members reached consensus.
Checklist: The final checklist has 21 entries in 4 categories: measure details, administration, scoring, and reporting. Most entries (11) specify necessary measure-specific details including version number and administration language(s). Administration (4 entries) reminds authors to include details such as use of proxy respondents and the assessment platform. Scoring (3 entries) is necessary to ensure replication and cross-study comparisons. Reporting (3 entries) reminds authors to always report scores on the T-score metric.

Conclusion
Consistent documentation is necessary to ensure transparent and reproducible methods and support the accumulation of evidence across studies. This checklist promotes standardization and completeness in documentation for ASCQ-Me, Neuro-QoL, PROMIS, and NIH Toolbox measures.
Questioning the status of aberrant speech patterns as psychiatric symptoms
Authors: Tan Eric J. , Rossell Susan L. 
Published: March 2020

SummarySpeech disturbances manifest in various psychiatric conditions and demonstrate temporal variability in relation to acute and stable symptom periods. They can be externally assessed, which facilitates their potential use as an objective marker of illness stage. Continued research will have positive implications for diagnostics and long-term management in clinical settings.
Machine Learning and Mechanistic Modeling for Prediction of Metastatic Relapse in Early-Stage Breast Cancer
Authors: Nicolò Chiara , Périer Cynthia , Prague Melanie , Bellera Carine , MacGrogan Gaëtan , Saut Olivier , Benzekry Sébastien 
Published: March 2020

PURPOSE For patients with early-stage breast cancer, predicting the risk of metastatic relapse is of crucial importance. Existing predictive models rely on agnostic survival analysis statistical tools (eg, Cox regression). Here we define and evaluate the predictive ability of a mechanistic model for time to distant metastatic relapse. METHODS The data we used for our model consisted of 642 patients with 21 clinicopathologic variables. A mechanistic model was developed on the basis of two intrinsic mechanisms of metastatic progression: growth (parameter α) and dissemination (parameter μ). Population statistical distributions of the parameters were inferred using mixed-effects modeling. A random survival forest analysis was used to select a minimal set of five covariates with the best predictive power. These were further considered to individually predict the model parameters by using a backward selection approach. Predictive performances were compared with classic Cox regression and machine learning algorithms. RESULTS The mechanistic model was able to accurately fit the data. Covariate analysis revealed statistically significant association of Ki67 expression with α ( P = .001) and EGFR expression with μ ( P = .009). The model achieved a c-index of 0.65 (95% CI, 0.60 to 0.71) in cross-validation and had predictive performance similar to that of random survival forest (95% CI, 0.66 to 0.69) and Cox regression (95% CI, 0.62 to 0.67) as well as machine learning classification algorithms. CONCLUSION By providing informative estimates of the invisible metastatic burden at the time of diagnosis and forward simulations of metastatic growth, the proposed model could be used as a personalized prediction tool for routine management of patients with breast cancer.
Kinetically Protected Carbon-Bridged Oligo(p-phenylenevinylene) Derivatives for Blue Color Amplified Spontaneous Emission
Authors: Bonal Víctor , Morales-Vidal Marta , Boj Pedro G , Villalvilla José M , Quintana José A , Lin Naiti , Watanabe Shoya , Tsuji Hayato , Nakamura Eiichi , Díaz-García María A 
Published: March 2020

Abstract
Carbon-bridged oligo(p-phenylenevinylene)s (COPVn with repeating unit n = 1–6) have demonstrated great success as laser dyes for thin-film organic lasers. The excellent photostability observed in the longer homologues is, however, not present in the blue-emitting shorter compounds COPV1 and COPV2, attributed to the unprotected terminal positions that can degrade by photoreaction in the excited state. Here we report the synthesis of various COPV1 and COPV2 derivatives functionalized at the terminal positions with two types of sterically bulky protecting substituents: Tip (2,4,6-triisopropylphenyl) and tert-butyl (t-Bu) groups. Such molecular designs aim at preventing such photodegradation processes and thus to improve their stability. The efficacy of kinetic isotope effect for stabilization is also examined for COPV2, by the addition at terminal positions of deuterium atoms. Absorption, photoluminescence (PL), including PL quantum yield, and amplified spontaneous emission (ASE) studies have been conducted in polystyrene films doped with each of the derivatives. Significant and slight improvements of the ASE photostability are observed for the compounds with Tip groups and deuterium, respectively. Installation of substituents slightly affects the ASE wavelength within the blue spectral region, that is 385–413 nm and 462–474 nm, for COPV1 and COPV2, respectively.
Femoral shaft fractures in children with non-ambulatory neuromuscular disorders can be effectively treated using flexible intramedullary nails
Authors: Siddiqui Ali A. , Illingworth Kenneth D. , Abousamra Oussama A. , Meisel Erin M. , Kay Robert M. 
Published: March 2020

Purpose There is little information in the literature regarding flexible intramedullary nails (FIN) for treating femur fractures in children with neuromuscular disorders. The purpose of this study is to investigate the outcomes of FIN for femoral shaft fractures in non-ambulatory children with neuromuscular disorders. Methods A retrospective review was conducted on patients with femur fractures at a paediatric hospital between 2004 and 2018. Inclusion criteria were femoral shaft fracture treated with FIN. Outcomes were compared between patients with neuromuscular disorders (NM group) and a control group of those without neuromuscular disorders. Results A total of 37 patients with 37 femoral shaft fractures were studied (12 patients in the NM group and 25 in the control group). All NM group patients were non-ambulatory at baseline. Fractures were length stable in all 25 patients in the control group and in 2/12 (17%) patients in the NM group. All fractures healed in both groups. Three complications (all nail migrations) requiring reoperation before fracture union occurred in the NM group, yielding a major complication rate of 25% (3/12) in the NM group versus 0% (0/25) in controls (p = 0.03). Angular deformity occurred in 5/12 (42%) NM group patients and 1/25 (4%) control group patient (p = 0.009); none required reoperation. Conclusion Femur fractures in non-ambulatory children with neuromuscular disorders can be successfully treated with FIN. Angular deformities are common in this population, but had no functional impact in the non-ambulatory NM group patients. Surgeons must also be vigilant for implant prominence and skin breakdown in these patients. Level of evidence III