bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers
Authors: Nascimento Emmani B. M. , Hangelbroek Roland W. J. , Hooiveld Guido J. E. J. , Hoeks Joris , Van Marken Lichtenbelt Wouter D. , Hesselink Matthijs H. C. , Schrauwen Patrick , Kersten Sander 
Published: September 2020

Abstract
Background
Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training.

Methods
To investigate if cold acclimation and exercise training overlap in the molecular adaptive response in skeletal muscle, we performed transcriptomics analysis on vastus lateralis muscle collected from human subjects before and after 10 days of cold acclimation, as well as before and after a 12-week exercise training intervention.

Results
Cold acclimation altered the expression of 756 genes (422 up, 334 down, P < 0.01), while exercise training altered the expression of 665 genes (444 up, 221 down, P < 0.01). Principal Component Analysis, Venn diagram, similarity analysis and Rank–rank Hypergeometric Overlap all indicated significant overlap between cold acclimation and exercise training in upregulated genes, but not in downregulated genes. Overlapping gene regulation was especially evident for genes and pathways associated with extracellular matrix remodeling. Interestingly, the genes most highly induced by cold acclimation were involved in contraction and in signal transduction between nerve and muscle cells, while no significant changes were observed in genes and pathways related to insulin signaling or glucose metabolism.

Conclusions
Overall, our results indicate that cold acclimation and exercise training have overlapping effects on gene expression in human skeletal muscle, but strikingly these overlapping genes are designated to pathways related to tissue remodeling rather than metabolic pathways.
Inducible intracellular membranes: molecular aspects and emerging applications
Authors: Royes Jorge , Biou Valérie , Dautin Nathalie , Tribet Christophe , Miroux Bruno 
Published: September 2020

AbstractMembrane remodeling and phospholipid biosynthesis are normally tightly regulated to maintain the shape and function of cells. Indeed, different physiological mechanisms ensure a precise coordination between de novo phospholipid biosynthesis and modulation of membrane morphology. Interestingly, the overproduction of certain membrane proteins hijack these regulation networks, leading to the formation of impressive intracellular membrane structures in both prokaryotic and eukaryotic cells. The proteins triggering an abnormal accumulation of membrane structures inside the cells (or membrane proliferation) share two major common features: (1) they promote the formation of highly curved membrane domains and (2) they lead to an enrichment in anionic, cone-shaped phospholipids (cardiolipin or phosphatidic acid) in the newly formed membranes. Taking into account the available examples of membrane proliferation upon protein overproduction, together with the latest biochemical, biophysical and structural data, we explore the relationship between protein synthesis and membrane biogenesis. We propose a mechanism for the formation of these non-physiological intracellular membranes that shares similarities with natural inner membrane structures found in α-proteobacteria, mitochondria and some viruses-infected cells, pointing towards a conserved feature through evolution. We hope that the information discussed in this review will give a better grasp of the biophysical mechanisms behind physiological and induced intracellular membrane proliferation, and inspire new applications, either for academia (high-yield membrane protein production and nanovesicle production) or industry (biofuel production and vaccine preparation).
Improving public hospital efficiency and fiscal space implications: the case of Mauritius
Authors: Nundoochan Ajoy 
Published: September 2020

Abstract
Background
General Government Health Expenditure (GGHE) in Mauritius accounted for only 10% of General Government Expenditure for the fiscal year 2018. This is less than the pledge taken under the Abuja 2001 Declaration to allocate at least 15% of national budget to the health sector. The latest National Health Accounts also urged for an expansion in the fiscal space for health. As public hospitals in Mauritius absorb 70% of GGHE, maximising returns of hospitals is essential to achieve Universal Health Coverage. More so, as Mauritius is bracing for its worst recession in 40 years in the aftermath of the COVID-19 pandemic public health financing will be heavily impacted. A thorough assessment of hospital efficiency and its implications on effective public health financing and fiscal space creation is, therefore, vital to inform ongoing health reform agenda.

Objectives
This paper aims to examine the trend in hospital technical efficiency over the period 2001–2017, to measure the elasticity of hospital output to changes in inputs variables and to assess the impact of improved hospital technical efficiency in terms of fiscal space creation.

Methods
Annual health statistics released by the Ministry of Health and Wellness and national budget of the Ministry of Finance, Economic Planning and Development were the principal sources of data. Applying Stochastic Frontier Analysis, technical efficiency of public regional hospitals was estimated under Cobb–Douglas, Translog and Multi-output distance functions, using STATA 11. Hospital beds, doctors, nurses and non-medical staff were used as input variables. Output variable combined inpatients and outpatients seen at Accident Emergency, Sorted and Unsorted departments. Efficiency scores were used to determine potential efficiency savings and fiscal space creation.

Findings
Mean technical efficiency scores, using the Cobb Douglas, Translog and Multi-output functions, were estimated at 0.83, 0.84 and 0.89, respectively. Nurses and beds are the most important factors in hospital production, as a 1% increase in the number of beds and nurses, result in an increase in hospital outputs by 0.73 and 0.51%, respectively. If hospitals are to increase their inputs by 1%, their outputs will increase by 1.16%. Hospital output process has an increasing return to scale. With technical efficiencies improving to scores of 0.95 and 1.0 in 2021–2022, potential savings and fiscal space creation at hospital level, would amount to MUR 633 million (US$ 16.2 million) and MUR 1161 million (US$ 29.6 million), respectively.

Conclusion
Fiscal space creation through full technical efficiency, is estimated to represent 8.9 and 9.2% of GGHE in fiscal year 2021–2022 and 2022–2023, respectively. This will allow without any restrictions the funding of the national response for HIV, vaccine preventable diseases as well as building a resilient health system to mitigate impact of emerging infectious diseases as experienced with COVID-19.
Factors affecting health-related quality of life in patients with skin disease: cross-sectional results from 8,789 patients with 16 skin diseases
Authors: He Zehui , Marrone Gaetano , Ou Aihua , Liu Hongxia , Ma Lin , Huang Ying , Li Yongmei , Sun Liyun , Bai Yanping , Liu Wali , Zha Xushan , Lu Chuanjian 
Published: September 2020

Abstract
Background
Many previous studies have reported factors that contribute to health-related quality of life (HRQoL) for a single skin disease. However, little is known about generalized factors associated with HRQoL across skin diseases. The objective of this study was to investigate overall HRQoL, and to identify factors related to severely impaired HRQoL among patients with 16 different skin diseases.

Methods
A cross-sectional study of 9845 patients with skin disease was conducted in 9 hospitals in China. HRQoL was assessed with the Chinese version of the Skindex-29 which measures dermatology-specific health along three domains (symptoms, emotions and functioning). With the published Skindex-29 cut-off scores for severely impaired HRQoL, logistic regression models assessed the relationship between severely impaired HRQoL and demographic/clinical characteristics, with adjustments for different skin diseases. To guarantee the models’ convergence, 16 skin diseases with frequencies of at least 100 were included, and the sample size was 8789.

Results
Emotions was the most impaired aspect of HRQoL. Co-existing chronic diseases, 3 years or longer duration, and more severity were identified as associated factors for severely impaired HRQoL for each Skindex-29 domain, and for the aggregate. Being female, under 45 years old, and consuming alcohol were associated with a severely impaired emotion domain; Lack of exercise and smoking were associated with severely impaired symptoms and function domains, respectively.

Conclusions
Skin diseases can affect many facets of HRQoL, but the emotional impairment deserves more attention. In addition to skin disease severity, this study shows that other chronic diseases and long duration are correlated with severely impaired HRQoL for patients with 16 clinical common skin diseases. This suggests the need for increased awareness in treating skin disease as a chronic disease. It also suggests that disease management decisions should consider HRQoL improvement, especially emotional conditions, when making management decisions.
Measuring positive mental health and flourishing in Denmark: validation of the mental health continuum-short form (MHC-SF) and cross-cultural comparison across three countries
Authors: Santini Ziggi Ivan , Torres-Sahli Manuel , Hinrichsen Carsten , Meilstrup Charlotte , Madsen Katrine R. , Rayce Signe Boe , Baker Melissa M. , Ten Have Margreet , Schotanus-Dijkstra Marijke , Koushede Vibeke 
Published: September 2020

Abstract
Background
The Mental Health Continuum–Short Form (MHC-SF) is a measure of positive mental health and flourishing, which is widely used in several countries but has not yet been validated in Denmark. This study aimed to examine its qualitative and quantitative properties in a Danish population sample and compare scores with Canada and the Netherlands.

Methods
Three thousand five hundred eight participants aged 16–95 filled out an electronic survey. Both the unidimensional and multidimensional aspects of the Danish MHC-SF were studied through bifactor modelling. Cognitive interviews examined face validity and usability.

Results
The general score of the Danish MHC-SF was reliable for computing unit-weighted composite scores, as well as using a bifactor model to compute general factor scores or measurement models in an SEM context. Nonetheless, subscale scores were unreliable, explaining very low variance beyond that explained by the general factor. The participants of the qualitative interviews observed problems with wording and content of the items, especially from the social subscale. The general score correlated with other scales as expected. We found substantial variation in flourishing prevalence rates between the three cultural settings.

Conclusions
The Danish MHC-SF produced reliable general scores of well-being. Most of the issues observed regarding the subscale scores have been shown in previous research in other contexts. The further analysis of indices of the bifactor model and the inclusion of qualitative interviews allowed for a better understanding of the possible sources of problems with the questionnaire’s subscales. The use of subscales, the substantive understanding of the general score, as well as the operationalization of the state of flourishing, require further study.
Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report)
Authors: Dell’Anno Irene , Barone Elisa , Mutti Luciano , Rassl Doris M. , Marciniak Stefan J. , Silvestri Roberto , Landi Stefano , Gemignani Federica 
Published: September 2020

Abstract
Background
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the pleura, mainly related to asbestos exposure. As in other solid tumors, malignant cells exhibit high glucose uptake and glycolytic rates with increased lactic acid efflux into the interstitial space. Lactate transport into and out of cells, crucial to maintaining intracellular pH homeostasis and glycolysis, is carried out by monocarboxylate transporters (MCTs) and the chaperone basigin (CD147). We set out to examine the clinical significance of basigin, MCT1 and MCT4 in the context of MPM and to evaluate their expression in relation to the evolution of the disease.

Methods
We used immunohistochemistry to measure the expression of basigin, MCT1 and MCT4 in a cohort of 135 individuals with MPM compared to a series of 15 non-MPM pleura specimens. Moreover, by Kaplan–Meier and Cox analyses we evaluated whether an expression over the average of these markers could be associated with the patients’ overall survival (OS).

Results
We detected positive staining of basigin, MCT1, and MCT4 in most MPM specimens. In particular, MCT4 was always positive in malignant tissues but undetectable in the 4 normal pleural specimens incorporated within the tissue microarray. This was confirmed in the additional series of 15 normal pleural samples. Moreover, MCT4 expression was significantly associated with reduced OS.

Conclusion
In this study, the tissue expression of basigin did not prove to be exploitable as a diagnostic or prognostic marker for MPM patients. The expression of MCT1 was not informative either, being tightly correlated with that of basigin. However, the expression of MCT4 showed promise as a diagnostic/therapeutic and prognostic biomarker.
A hypoxia-related signature for clinically predicting diagnosis, prognosis and immune microenvironment of hepatocellular carcinoma patients
Authors: Zhang Baohui , Tang Bufu , Gao Jianyao , Li Jiatong , Kong Lingming , Qin Ling 
Published: September 2020

Abstract
Background
Hypoxia plays an indispensable role in the development of hepatocellular carcinoma (HCC). However, there are few studies on the application of hypoxia molecules in the prognosis predicting of HCC. We aim to identify the hypoxia-related genes in HCC and construct reliable models for diagnosis, prognosis and recurrence of HCC patients as well as exploring the potential mechanism.

Methods
Differentially expressed genes (DEGs) analysis was performed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and four clusters were determined by a consistent clustering analysis. Three DEGs closely related to overall survival (OS) were identified using Cox regression and LASSO analysis. Then the hypoxia-related signature was developed and validated in TCGA and International Cancer Genome Consortium (ICGC) database. The Gene Set Enrichment Analysis (GSEA) was performed to explore signaling pathways regulated by the signature. CIBERSORT was used for estimating the fractions of immune cell types.

Results
A total of 397 hypoxia-related DEGs in HCC were detected and three genes (PDSS1, CDCA8 and SLC7A11) among them were selected to construct a prognosis, recurrence and diagnosis model. Then patients were divided into high- and low-risk groups. Our hypoxia-related signature was significantly associated with worse prognosis and higher recurrence rate. The diagnostic model also accurately distinguished HCC from normal samples and nodules. Furthermore, the hypoxia-related signature could positively regulate immune response. Meanwhile, the high-risk group had higher fractions of macrophages, B memory cells and follicle-helper T cells, and exhibited higher expression of immunocheckpoints such as PD1and PDL1.

Conclusions
Altogether, our study showed that hypoxia-related signature is a potential biomarker for diagnosis, prognosis and recurrence of HCC, and it provided an immunological perspective for developing personalized therapies.
Genetic and environmental determinants of human TCR repertoire diversity
Authors: Krishna Chirag , Chowell Diego , Gönen Mithat , Elhanati Yuval , Chan Timothy A. 
Published: September 2020

AbstractT cell discrimination of self and non-self is the foundation of the adaptive immune response, and is orchestrated by the interaction between T cell receptors (TCRs) and their cognate ligands presented by major histocompatibility (MHC) molecules. However, the impact of host immunogenetic variation on the diversity of the TCR repertoire remains unclear. Here, we analyzed a cohort of 666 individuals with TCR repertoire sequencing. We show that TCR repertoire diversity is positively associated with polymorphism at the human leukocyte antigen class I (HLA-I) loci, and diminishes with age and cytomegalovirus (CMV) infection. Moreover, our analysis revealed that HLA-I polymorphism and age independently shape the repertoire in healthy individuals. Our data elucidate key determinants of human TCR repertoire diversity, and suggest a mechanism underlying the evolutionary fitness advantage of HLA-I heterozygosity.
Locoregional recurrence patterns in women with breast cancer who have not undergone post-mastectomy radiotherapy
Authors: Zhao Xuran , Tang Yu , Wang Shulian , Yang Yong , Fang Hui , Wang Jianyang , Jing Hao , Zhang Jianghu , Sun Guangyi , Chen Siye , Jin Jing , Song Yongwen , Liu Yueping , Chen Bo , Qi Shunan , Li Ning , Tang Yuan , Lu Ningning , Ren Hua , Li Yexiong 
Published: September 2020

Abstract
Background
To analyze the patterns of locoregional recurrence in breast cancer patients after mastectomy.

Methods
The retrospective study included 7073 women with breast cancer without post-mastectomy radiotherapy: 4604 (65.1%) had pT1–2 N0 disease (low risk); 2042 (28.9%), pT1–2 N1 (intermediate risk); and 427 (6.0%), pT3–4 and/or pN2–3, or pT1–2 N1 after neoadjuvant chemotherapy (high risk). The distribution of cumulative locoregional recurrence was analyzed. The local recurrence and regional recurrence rates were estimated by the Kaplan-Meier method, and differences were compared with the log-rank test. Multivariate analysis was performed using Cox logistic regression analysis.

Results
In the median follow-up of 63.0 months, 469 patients had locoregional recurrence: chest wall recurrence in 238 (50.7%) cases, supraclavicular/infraclavicular nodes in 236 (50.3%) cases, axilla in 92 (19.6%), and internal mammary nodes in 50 (10.7%) cases. The 5-year local recurrence and regional recurrence rates were 2.5 and 4.4%, respectively. Subgroup analysis of the three risk groups and five molecular subtypes (luminal A, luminal B-Her2 negative, luminal B-Her2 positive, Her2-enriched, and triple negative) also showed that the chest wall and supraclavicular/infraclavicular nodes were the most common recurrence sites. Age, tumor location, T stage, N stage, and hormone receptor status were independent prognostic factors for both local recurrence and regional recurrence (p < 0.05).

Conclusions
The chest wall and supraclavicular/infraclavicular nodes are common sites of locoregional recurrence in breast cancer, irrespective of disease stage or molecular subtype, and the prognostic factors for local recurrence and regional recurrence are similar. Therefore, chest wall and supraclavicular/infraclavicular nodes irradiation should always be considered in post-mastectomy radiotherapy.
Finite element modeling of proximal femur with quantifiable weight-bearing area in standing position
Authors: Yang Peng , Lin Tian-Ye , Xu Jing-Li , Zeng Hui-Yu , Chen Da , Xiong Bing-Lang , Pang Feng-Xiang , Chen Zhen-Qiu , He Wei , Wei Qiu-Shi , Zhang Qing-Wen 
Published: September 2020

Abstract

The positional distribution and size of the weight-bearing area of the femoral head in the standing position as well as the direct active surface of joint force can directly affect the result of finite element (FE) stress analysis. However, the division of this area was vague, imprecise, and un-individualized in most studies related to separate FE models of the femur. The purpose of this study was to quantify the positional distribution and size of the weight-bearing area of the femoral head in standing position by a set of simple methods, to realize individualized reconstruction of the proximal femur FE model.

Five adult volunteers were recruited for an X-ray and CT examination in the same simulated bipedal standing position with a specialized patented device. We extracted these image data, calculated the 2D weight-bearing area on the X-ray image, reconstructed the 3D model of the proximal femur based on CT data, and registered them to realize the 2D weight-bearing area to 3D transformation as the quantified weight-bearing surface. One of the 3D models of the proximal femur was randomly selected for finite element analysis (FEA), and we defined three different loading surfaces and compared their FEA results.

A total of 10 weight-bearing surfaces in 5 volunteers were constructed, and they were mainly distributed on the dome and anterolateral of the femoral head with a crescent shape, in the range of 1218.63–1,871.06 mm2. The results of FEA showed that stress magnitude and distribution in proximal femur FE models among three different loading conditions had significant differences, and the loading case with the quantized weight-bearing area was more in accordance with the physical phenomenon of the hip.

This study confirmed an effective FE modeling method of the proximal femur, which can quantify the weight-bearing area to define a more reasonable load surface setting without increasing the actual modeling difficulty.
HIV Nef enhances the expression of oncogenic c-MYC and activation-induced cytidine deaminase in Burkitt lymphoma cells, promoting genomic instability
Authors: Mdletshe Nontlantla , Nel Andrew , Shires Karen , Mowla Shaheen 
Published: September 2020

AbstractBackgroundNon-Hodgkin lymphoma is of high prevalence among HIV-infected people. In particular, the incidence of HIV-associated Burkitt lymphoma (BL) remains high despite the advent of Highly Active Anti-Retroviral Therapy. Recent evidence shows that serum-soluble HIV proteins can enhance oncogenesis, particularly in lymphoid tissues. This study sought to define the role of HIV protein Negative regulatory factor (Nef) in BL development by assessing its effect on key lymphoma driver genes.MethodsA recombinant Nef protein was used to assess changes in expressions of activation-induced cytidine deaminase (AICDA/AID) and c-MYC in B lymphocytes exposed extracellularly to the protein. Additionally, changes in the promoter activities of these genes were measured using a Nef-expressing cellular model and reporter assays. Confocal microscopy was used to observe c-MYC and AID expression and localization, and genomic integrity via the recruitment of phosphorylated γ-H2AX, in Nef-exposed cells.ResultsmRNA transcription ofc-MYCandAICDAwere significantly enhanced in lymphoma cells, up to 2-fold forc-MYCand up to 4-fold forAICDA, when exposed to varying concentrations of Nef (0–1000 ng/ml) and for different periods of time (3, 6 and 12 h). The protein expressions of AID and c-MYC followed a similar pattern and these effects were specific to BL but not lymphoblastoid cells. While the promoter activity ofc-MYCwas enhanced in the presence of Nef in a dose-dependent manner, the same was not observed forAICDA. Both AID and c-MYC accumulated within the cytoplasmic and nuclear spaces of Nef-exposed lymphoma cells, with a concomitant increase in DNA double strand breaks within the genome.ConclusionsExposure to HIV Nef leads to significant increases in AID and c-MYC, leading to genomic instability, potentially enhancing the oncogenic potential of Burkitt lymphoma. Our findings align with that of others to show that HIV proteins can directly contribute to the development and pathogenesis of HIV-associated lymphoma and accounts for the elevated incidence of BL observed in the HIV-infected population.