bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in the management of haemophilia: emerging treatments and their mechanisms
Authors: Okaygoun Dide , Oliveira Danielle D. , Soman Sooriya , Williams Riccardo 
Published: September 2021

AbstractMainstay haemophilia treatment, namely intravenous factor replacement, poses several clinical challenges including frequent injections due to the short half-life of recombinant factors, intravenous administration (which is particularly challenging in those with difficult venous access), and the risk of inhibitor development. These impact negatively upon quality of life and treatment compliance, highlighting the need for improved therapies. Several novel pharmacological therapies developed for haemophilia aim to rebalance the clotting cascade and potentially circumvent the aforementioned challenges. These therapies utilise a range of different mechanisms, namely: the extension of the circulating half-life of standard recombinant factors; the mimicking of factor VIII cofactor activity; rebalancing of coagulation through targeting of natural anticoagulants such as antithrombin and tissue factor pathway inhibitor; and inducing the production of endogenous factors with gene therapy. These therapies carry the potential of revolutionising haemophilia treatment by alleviating the current challenges presented by mainstay factor replacement. This review will provide an overview of the key trial findings related to novel therapies based on the mechanisms described above.
Effect of diabetes mellitus on the development of left ventricular contractile dysfunction in women with heart failure and preserved ejection fraction
Authors: Shi Ke , Yang Meng-Xi , Huang Shan , Yan Wei-Feng , Qian Wen-Lei , Li Yuan , Guo Ying-Kun , Yang Zhi-Gang 
Published: September 2021

Abstract
Background
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with sex-specific pathophysiology. Estrogen deficiency is believed to be responsible for the development of HFpEF in women. However, estrogen deficiency does not seem to be completely responsible for the differences in HFpEF prevalence between sexes. While diabetes mellitus (DM) frequently coexists with HFpEF in women and is associated with worse outcomes, the changes in myocardial contractility among women with HFpEF and the DM phenotype is yet unknown. Therefore, we aimed to investigate sex-related differences in left ventricular (LV) contractility dysfunction in HFpEF comorbid with DM.

Methods
A total of 224 patients who underwent cardiac cine MRI were included in this study. Sex-specific differences in LV structure and function in the context of DM were determined. LV systolic strains (global longitudinal strain [GLS], circumferential strain [GCS] and radial strain [GRS]) were measured using cine MRI. The determinants of impaired myocardial strain for women and men were assessed.

Results
The prevalence of DM did not differ between sexes (p > 0.05). Despite a similar LV ejection fraction, women with DM demonstrated a greater LV mass index than women without DM (p = 0.023). The prevalence of LV geometry patterns by sex did not differ in the non-DM subgroup, but there was a trend toward a more abnormal LV geometry in women with DM (p = 0.072). The magnitudes of systolic strains were similar between sexes in the non-DM group (p > 0.05). Nevertheless, in the DM subgroup, there was significant impairment in women in systolic strains compared with men (p < 0.05). In the multivariable analysis, DM was associated with impaired systolic strains in women (GLS [β = 0.26; p = 0.007], GCS [β = 0.31; p < 0.001], and GRS [β = −0.24; p = 0.016]), whereas obesity and coronary artery disease were associated with impaired systolic strains in men (p < 0.05).

Conclusions
Women with DM demonstrated greater LV contractile dysfunction, which indicates that women with HFpEF comorbid with DM have a high-risk phenotype of cardiac failure that may require more aggressive and personalized medical treatment.
The role of XBP-1-mediated unfolded protein response in colorectal cancer progression-a regulatory mechanism associated with lncRNA-miRNA-mRNA network
Authors: Wang Yong , Zhang Jingyu , Zheng Shuang 
Published: September 2021

Abstract
Background
We aim to identify the expression and analyze the molecular action of dysregulated lncRNA-miRNA mediated by XBP-1 in colorectal cancer (CRC).

Methods
Here, we identified XBP-1-mediated dysregulated lncRNAs and miRNAs in CRC by bioinformatics analysis. The expression level of lncRNAs and miRNA was measured using quantitative real time PCR, and the expression of XBP-1, as well as apoptosis-related proteins, were detected by western blot. CCK-8 and TUNEL assays were performed to determine cell proliferation and apoptosis, respectively. Luciferase reporter assay was conducted to verify the binding relationship among lncRNA-miRNA-XBP-1. BALB/c nude mice were inoculated subcutaneously with HCT116 cells to establish tumor-bearing mice model. Histological analysis was carried out by HE staining and immunohistochemical staining.

Results
Six downregulated lncRNAs (SLFNL1-AS1, KCNQ1OT1, NEAT1, XIST, AC016876.2, AC026362.1), four dysregulated miRNAs (miR-500a-3p, miR-370-3p, miR-2467-3p, miR-512-3p) and upregulated XBP-1 were identified in CRC cell lines. Gain- and loss-of-function experiments showed that overexpression of KCNQ1OT1/XIST promoted cell proliferation and suppressed cell apoptosis. In addition, overexpression of KCNQ1OT1/XIST partly abolished the inhibitory effects of XBP-1u knockdown or tunicamycin, an activator of endoplasmic reticulum stress, on CRC cell viability loss and apoptosis. Furthermore, KCNQ1OT1/XIST aggravated tumor growth in vivo by regulating endoplasmic reticulum stress and cell apoptosis.

Conclusions
This study has constructed lncRNA-miRNA-mRNA networks based on XBP-1 in CRC, and disclosed the regulatory mechanism of action, providing a set of pivotal biomarkers for future molecular investigation and targeted treatment of CRC.
The association between occupational factors, depression, and health-related quality of life in military women in the Republic of Korea: a cross-sectional study
Authors: Kwon Eunji , Park Jeongok , Kim Sue , Lee Kyung Hee 
Published: September 2021

Abstract
Background
Health-related quality of life (HRQOL) is an important concept to consider both individuals' ability to manage their daily lives and health status across the lifespan. Despite this variable's importance, there is a lack of clarification on the factors associated with HRQOL, especially for military women. The aim of this study was to examine factors associated with HRQOL of military women in the Republic of Korea (ROK) Army.

Methods
This cross-sectional study included 196 participants who were currently within their 5-year service period. HRQOL was measured by the Korean version of the Short-Form 36 Health Survey Questionnaire version 2.0 (SF-36v2), and depression was assessed using the Korean version of the Patient Health Questionnaire-9 (PHQ-9). Differences in HRQOL according to general and occupational factors were analyzed using the independent t-test and analysis of variance (ANOVA). Multiple linear regression analysis was performed to identify factors associated with the HRQOL of women serving as military junior officers.

Results
The mean score for the physical component summary (PCS) of SF-36v2 was 56.0 ± 5.8, and that for the mental component summary (MCS) of SF-36v2 was 47.2 ± 10.0. For depression, the mean score was 5.4 ± 5.2, whereas 19.4% of the participants scored more than 10 out of 27 points, which means moderate to severe. No variables showed statistically significant relationships with the PCS. However, military women showed a lower score for MCS when they were officers (adjusted β = − 3.52; 95% CI = − 5.47, − 1.58), had higher perceived stress (adjusted β = − 0.62, 95% CI = − 0.83, − 0.41), and a higher score for depression (adjusted β = − 0.86, 95% CI = − 1.10, − 0.63).

Conclusions
Although depression levels were not severe, it was a significant factor of HRQOL. Stress and depression were found to be significant factors associated with the MCS in military women. Therefore, to improve their HRQOL, the ROK Army should provide early screening, intervention, and management program for high-risk military women. In addition, an appropriate organizational atmosphere within the military must be created to promote such programs.
Effect of 2020 containment strategies on trauma workflow in Ile-de-France region: another benefit of lockdown?
Authors: Moyer Jean-Denis , Abback Paer-Selim , Hamada Sophie , Martinez Thibault , Werner Marie , James Arthur ,   the Traumabase®Group
Published: September 2021

Abstract
Background
During the SARS-CoV-2 pandemic, the French Government imposed various containment strategies, such as severe lockdown (SL) or moderate lockdown (ML). The aim of this study was to evaluate the effect of both strategies on severe trauma admissions and ICU capacity in Ile-de-France region (Paris Area).

Main text
We conducted a multicenter cohort-based observational study from 1stJanuary 2017 to 31th December 2020, including all consecutive trauma patients admitted to the trauma centers of Ile-de-France region participating in the national registry (Traumabase®). Two periods were defined, the “non-pandemic period” (NPP) from 2017 to 2019, and the “pandemic period” (PP) concerning those admitted in 2020. The number of ICU beds released during 2020 pandemic period (overall period, SL and ML) was estimated by multiplying difference in trauma admissions by the median length of stay during the same week of pandemic period (ICU day-beds in 2020).
A 15% yearly reduction of trauma patients was observed during the PP, associated with the release of 6422 ICU day-beds in 2020. During SL and ML, the observed decrease in trauma admission was respectively 49 and 39% compared with similar dates of the NPP. The number of beds released was 1531 days-beds in SL and 679 day-beds in ML. Those reductions respectively accounted for 4.5 and 6.0% of the overall ICU admission for COVID-19 in Ile-de-France.

Conclusion
The lockdown strategies during pandemic resulted in a reduction of severe trauma admissions. In addition to the social distancing effect, lockdown strategies freed up an important number of ICU beds in trauma centers, available for severe COVID-19 patients.
Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence
Authors: Menzies Georgina E. , Prior Ian A. , Brancale Andrea , Reed Simon H. , Lewis Paul D. 
Published: September 2021

Abstract
Background
Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14.

Results
Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts.

Conclusions
We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPDE, are due to the effect of the interaction methyl group at the C5 position of the thymine base in the KRAS sequence with the BPDE carcinogen investigated causing increased distortion. We further suggest methylated cytosine would have a similar effect, showing the importance of methylation in cancer development.
Quantitative evaluation of interim positron emission tomography in peripheral T-cell lymphoma
Authors: Kurch Lars , Dührsen Ulrich , Hüttmann Andreas , Georgi Thomas W. , Sabri Osama , Kluge Regine , Hasenclever Dirk 
Published: September 2021

Abstract
Background
Interim [18F]fluoro-deoxyglucose-positron emission tomography predicts outcome in peripheral T-cell lymphoma (PTCL). We compared two quantitative evaluation methods.

Methods
Interim scans from 43 patients with anaplastic lymphoma kinase-negative PTCL from the ‘Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas’ trial were re-analyzed by qPET (relating residual lymphoma-related uptake to liver uptake) and ∆SUVmax (relating interim scan to baseline scan). The endpoint was progression-free survival.

Results
qPET and ∆SUVmax were closely correlated (Pearson’s r = 0.627). Up to the 60th percentile of values ranked by increasing residual activity, the positive predictive value for progression or death increased from 60 to 95%, with stable negative predictive values (NPV) of 60%. Beyond the 60th percentile, the NPV decreased to 40%. qPET ≥ 2 and ∆SUVmax < 50% identified high-risk populations comprising 41.9% and 39.5% of patients, with 3-year progression-free survival rates of 5.6% (95% confidence interval, 0.8–37.3) and 0%, respectively, as compared to 63.7% (47.4–85.8) and 61.3% (45.1–83.3) in low-risk patients.

Conclusions
qPET and ∆SUVmax identify large fractions of PTCL patients destined to experience treatment failure. qPET may be preferred because it requires a single PET scan, halving the diagnostic effort.
Disruptive innovation in a dynamic environment: a winning strategy? An illustration through the analysis of the yoghurt industry in Algeria
Authors: Chemma Nawal 
Published: September 2021

AbstractDisruptive strategies have only been studied in stable environments. To overcome this limitation, this article aims to show through an in-depth study of the main actors in the yoghurt industry in Algeria that these strategies are possible in a dynamic environment. This research was carried out on the basis of an exploratory qualitative study. We have focused our efforts on two types of players, including new entrants and incumbent businesses.Our results show that the strong factors of the competitive dynamics pushed companies and industries to undertake disruptive innovation, which strategy became an indispensable element to survive and succeed for all the actors in the industry. Overall, our study indicates that the link between the competitive dynamics and disruptive innovation is not only in need of, but is deserving of, more consideration.
Fibroblast growth factor 21 in dairy cows: current knowledge and potential relevance
Authors: Eder Klaus , Gessner Denise K. , Ringseis Robert 
Published: September 2021

AbstractFibroblast growth factor 21 (FGF21) has been identified as an important regulator of carbohydrate and lipid metabolism, which plays an important role for metabolic regulation, particularly under conditions of energy deprivation or stress conditions. Dairy cows are subjected to a negative energy balance and various kinds of stress particularly during the periparturient phase and during early lactation. It has been shown that the plasma concentration of FGF21 in dairy cows is dramatically increased at parturition and remains high during the first weeks of lactation. This finding suggests that FGF21 might exert similar functions in dairy cows than in other species, such as mice or humans. However, the role of FGF21 in dairy cows has been less investigated so far. Following a brief summary of the previous findings about the function of FGF21 in humans and mice, the present review aims to present the current state of knowledge about the role of FGF21 in dairy cows. The first part of the review deals with the tissue localization of FGF21 and with conditions leading to an upregulation of FGF21 expression in the liver of dairy cows. In the second part, the influence of nutrition on FGF21 expression and the role of FGF21 for metabolic diseases in dairy cows is addressed. In the third part, findings of exogenous FGF21 application on metabolism in dairy cows are reported. Finally, the potential relevance of FGF21 in dairy cows is discussed. It is concluded that FGF21 might be of great importance for metabolic adaptation to negative energy balance and stress conditions in dairy cows. However, further studies are needed for a better understanding of the functions of FGF21 in dairy cows.
Changes in the b value in and around the focal areas of the M6.9 and M6.8 earthquakes off the coast of Miyagi prefecture, Japan, in 2021
Authors: Nanjo K. Z. , Yoshida A. 
Published: September 2021

AbstractWe investigated changes in the b value of the Gutenberg–Richter’s law in and around the focal areas of earthquakes on March 20 and on May 1, 2021, with magnitude (M) 6.9 and 6.8, respectively, which occurred off the Pacific coast of Miyagi prefecture, northeastern Japan. We showed that the b value in these focal areas had been noticeably small, especially within a few years before the occurrence of the M6.9 earthquake in its vicinity, indicating that differential stress had been high in the focal areas. The coseismic slip of the 2011 Tohoku earthquake seems to have stopped just short of the east side of the focus of the M6.9 earthquake. Furthermore, the afterslip of the 2011 Tohoku earthquake was relatively small in the focal areas of the M6.9 and M6.8 earthquakes, compared to the surrounding regions. In addition, the focus of the M6.9 earthquake was situated close to the border point where the interplate slip in the period from 2012 through 2021 has been considerably larger on the northern side than on the southern side. The high-stress state inferred by the b-value analysis is concordant with those characteristics of interplate slip events. We found that the M6.8 earthquake on May 1 occurred near an area where the b value remained small, even after the M6.9 quake. The ruptured areas by the two earthquakes now seem to almost coincide with the small-b-value region that had existed before their occurrence. The b value on the east side of the focal areas of the M6.9 and M6.8 earthquakes which corresponds to the eastern part of the source region of the 1978 off-Miyagi prefecture earthquake was consistently large, while the seismicity enhanced by the two earthquakes also shows a large b value, implying that stress in the region has not been very high.
Screening of single nucleotide polymorphisms among fuchs’ endothelial corneal dystrophy subjects in Malaysia
Authors: Ng Ker Hsin , Subrayan Visvaraja , Ramachandran Vasudevan , Ismail Fazliana 
Published: September 2021

Abstract
Background
The pathophysiology underlying Fuchs' Endothelial Corneal Dystrophy (FECD), especially in older individuals, remains unclear, with a genetic predisposition being reported as the single best predictor of the disease. Genetic studies have shown that several genes in various loci such as COL8A2, SLC4A11, TCF8/ZEB1 and TCF4 are associated with FECD in different populations and ethnicities. A case–control study was conducted to determine the association between genetic variants and FECD in a tertiary care setting in Malaysia. A total number of 12 patients with clinically diagnosed FECD and 12 age, gender and race matched control subjects were recruited. Extracted genomic DNA were genotyped using Infinium Global Screening Array (GSA)-24 version 1.0 BeadChip with iScan high-throughput system. Illumina GenomeStudio 2.0 Data Analysis and PLINK version 1.9 software were used to perform association tests and determine the distribution of obtained variants among the cases and controls.

Results
A significant novel genetic variant, rs11626651, a variant of the LOC105370676 gene or known as the LINC02320 gene, located at chromosome 14, has been identified as a suggestive association with FECD (p < 5 × 10−6). Further analysis in this study suggested that candidate genes such as COL8A2, ZEB1/TCF8, TCF4 and SLC4A11 had no significant associations with FECD.

Conclusions
The discovery of a novel variant may influence the underlying pathogenic basis of FECD in Malaysia. The current study is the first genetic study on FECD to use Infinium GSA. It is the first comprehensive report in Malaysia to provide genetic information of potential relevance to FECD, which may pave the way for new therapeutic strategies in the future. A detailed analysis with a larger sample size is recommended for further evaluation.
Insulin Increases Adipose Adiponectin in Pregnancy by Inhibiting Ubiquitination and Degradation: Impact of Obesity
Authors: Aye Irving L M H , Rosario Fredrick J , Kramer Anita , Kristiansen Oddrun , Michelsen Trond M , Powell Theresa L , Jansson Thomas 
Published: September 2021

Abstract

Context
Circulating adiponectin levels are decreased in pregnant women with obesity or gestational diabetes, and this is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms regulating adiponectin secretion from maternal adipose tissues in pregnancy are poorly understood.

Objective
We tested the hypothesis that obesity in pregnancy is associated with adipose tissue insulin resistance and increased adiponectin ubiquitination and degradation, caused by inflammation and endoplasmic reticulum (ER) stress.

Methods
Visceral adipose tissues were collected from lean and obese pregnant humans and mice. Total and ubiquitinated adiponectin, and markers of inflammation, ER stress, and insulin resistance were examined in adipose tissues. The role of insulin, inflammation, and ER stress in mediating adiponectin ubiquitination and degradation was examined using 3T3L-1 adipocytes.

Results
Obesity in pregnancy is associated with adipose tissue inflammation, ER stress, insulin resistance, increased adiponectin ubiquitination, and decreased total abundance of adiponectin. Adiponectin ubiquitination was increased in visceral fat of obese pregnant women as compared to lean pregnant women. We further observed that insulin prevents, whereas ER stress and inflammation promote, adiponectin ubiquitination and degradation in differentiated 3T3-L1 adipocytes.

Conclusion
We have identified adiponectin ubiquitination as a key mechanism by which obesity diminishes adiponectin secretion in pregnancy. This information will help us better understand the mechanisms controlling maternal insulin resistance and fetal growth in pregnancy and may provide a foundation for the development of strategies aimed at improving adiponectin production in pregnant women with obesity or gestational diabetes.
Obesity and Postmenopausal Hormone Receptor-positive Breast Cancer: Epidemiology and Mechanisms
Authors: Zuo Qianying , Band Shoham , Kesavadas Mrinali , Madak Erdogan Zeynep 
Published: September 2021

AbstractObesity is a potential risk for several cancers, including postmenopausal, hormone dependent breast cancers. In this review, we summarize recent studies on the impact of obesity on postmenopausal women’s health and discuss several mechanisms that were proposed to increase the risk of breast carcinogenesis.