bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDX2 inhibits epithelial–mesenchymal transition in colorectal cancer by modulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression
Authors: Yu Junhui , Li Shan , Xu Zhengshui , Guo Jing , Li Xiaopeng , Wu Yunhua , Zheng Jianbao , Sun Xuejun 
Published: November 2020

Abstract
Background
Emerging evidence suggests the involvement of caudal-related homoeobox transcription factor 2 (CDX2) in tumorigenesis of various cancers. Although CDX2 functions in cancer invasion and metastasis, fewer studies focus on the role of CDX2 during the induction of epithelial–mesenchymal transition (EMT) in colorectal cancer (CRC).

Methods
Immunohistochemical analysis of CDX2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of CDX2 in the invasion and metastasis of CRC.

Results
CDX2 was downregulated in CRC tissues and reduced CDX2 correlated with poor prognosis. Knockdown of CDX2 promoted colon cancer cell invasion in vitro and facilitated liver metastasis in vivo with inducing EMT phenotypes. Further investigation indicated that CDX2 retarded Akt and GSK-3β phosphorylation, and thereby diminished Snail expression, β-catenin stabilisation and nuclear translocation. The depletion of β-catenin neutralised the regulation of Slug and ZEB1 by CDX2 knockdown. Mechanistically, CDX2 antagonised PI3K/Akt activity in CRC by modulating PTEN expression. CDX2 directly bound to the promoter of PTEN and transactivated its expression.

Conclusions
Our study first uncovered that CDX2 inhibits EMT and metastasis of CRC by regulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.
The lingering mysteries of metastatic recurrence in breast cancer
Authors: Riggio Alessandra I. , Varley Katherine E. , Welm Alana L. 
Published: November 2020

AbstractDespite being the hallmark of cancer that is responsible for the highest number of deaths, very little is known about the biology of metastasis. Metastatic disease typically manifests after a protracted period of undetectable disease following surgery or systemic therapy, owing to relapse or recurrence. In the case of breast cancer, metastatic relapse can occur months to decades after initial diagnosis and treatment. In this review, we provide an overview of the known key factors that influence metastatic recurrence, with the goal of highlighting the critical unanswered questions that still need to be addressed to make a difference in the mortality of breast cancer patients.
The fibrotic and immune microenvironments as targetable drivers of metastasis
Authors: Boulter Luke , Bullock Esme , Mabruk Zeanap , Brunton Valerie G. 
Published: November 2020

AbstractAlthough substantial progress has been made over the past 40 years in treating patients with cancer, effective therapies for those who are diagnosed with advanced metastatic disease are still few and far between. Cancer cells do not exist in isolation: rather, they exist within a complex microenvironment composed of stromal cells and extracellular matrix. Within this tumour microenvironment exists an interplay between the two main stromal cell subtypes, cancer-associated fibroblasts (CAFs) and immune cells, that are important in controlling metastasis. A complex network of paracrine signalling pathways between CAFs, immune cells and tumour cells are involved at multiple stages of the metastatic process, from invasion and intravasation at the primary tumour site to extravasation and colonisation in the metastatic site. Heterogeneity and plasticity within stromal cell populations also contribute to the complexity. Although many of these processes are likely to be common to a number of metastatic sites, we will describe in detail the interplay within the liver, a preferred site of metastasis for many tumours. A greater understanding of these networks provides opportunities for the design of new therapeutic approaches for targeting the metastatic disease.
Legumain is a predictor of all-cause mortality and potential therapeutic target in acute myocardial infarction
Authors: Yang Hui , He Yuhu , Zou Pu , Hu Yilei , Li Xuping , Tang Liang , Zhu Zhaowei , Tai Shi , Tu Tao , Xiao Yichao , Chen Mingxian , Wu Chenlu , Zhou Shenghua 
Published: November 2020

AbstractThe prognostic impact of extracellular matrix (ECM) modulation and its regulatory mechanism post-acute myocardial infarction (AMI), require further clarification. Herein, we explore the predictive role of legumain—which showed the ability in ECM degradation—in an AMI patient cohort and investigate the underlying mechanisms. A total of 212 AMI patients and 323 healthy controls were enrolled in the study. Moreover, AMI was induced in mice by permanent ligation of the left anterior descending artery and fibroblasts were adopted for mechanism analysis. Based on the cut-off value for the receiver-operating characteristics curve, AMI patients were stratified into low (n = 168) and high (n = 44) plasma legumain concentration (PLG) groups. However, PLG was significantly higher in AMI patients than that in the healthy controls (median 5.9 μg/L [interquartile range: 4.2–9.3 μg/L] vs. median 4.4 μg/L [interquartile range: 3.2–6.1 μg/L],P < 0.001). All-cause mortality was significantly higher in the high PLG group compared to that in the low PLG group (median follow-up period, 39.2 months; 31.8% vs. 12.5%;P = 0.002). Multivariate Cox regression analysis showed that high PLG was associated with increased all-cause mortality after adjusting for clinical confounders (HR = 3.1, 95% confidence interval (CI) = 1.4–7.0,P = 0.005). In accordance with the clinical observations, legumain concentration was also increased in peripheral blood, and infarcted cardiac tissue from experimental AMI mice. Pharmacological blockade of legumain with RR-11a, improved cardiac function, decreased cardiac rupture rate, and attenuated left chamber dilation and wall thinning post-AMI. Hence, plasma legumain concentration is of prognostic value in AMI patients. Moreover, legumain aggravates cardiac remodelling through promoting ECM degradation which occurs, at least partially, via activation of the MMP-2 pathway.
Selecting the most important self-assessed features for predicting conversion to mild cognitive impairment with random forest and permutation-based methods
Authors: Gómez-Ramírez Jaime , Ávila-Villanueva Marina , Fernández-Blázquez Miguel Ángel 
Published: November 2020

AbstractAlzheimer’s Disease is a complex, multifactorial, and comorbid condition. The asymptomatic behavior in the early stages makes the identification of the disease onset particularly challenging. Mild cognitive impairment (MCI) is an intermediary stage between the expected decline of normal aging and the pathological decline associated with dementia. The identification of risk factors for MCI is thus sorely needed. Self-reported personal information such as age, education, income level, sleep, diet, physical exercise, etc. is called to play a key role not only in the early identification of MCI but also in the design of personalized interventions and the promotion of patients empowerment. In this study, we leverage a large longitudinal study on healthy aging in Spain, to identify the most important self-reported features for future conversion to MCI. Using machine learning (random forest) and permutation-based methods we select the set of most important self-reported variables for MCI conversion which includes among others, subjective cognitive decline, educational level, working experience, social life, and diet. Subjective cognitive decline stands as the most important feature for future conversion to MCI across different feature selection techniques.
A potential energy and mutual information based link prediction approach for bipartite networks
Authors: Kumar Purushottam , Sharma Dolly 
Published: November 2020

AbstractLink prediction in networks has applications in computer science, graph theory, biology, economics, etc. Link prediction is a very well studied problem. Out of all the different versions, link prediction for unipartite graphs has attracted most attention. In this work we focus on link prediction for bipartite graphs that is based on two very important concepts—potential energy and mutual information. In the three step approach; first the bipartite graph is converted into a unipartite graph with the help of a weighted projection, next the potential energy and mutual information between each node pair in the projected graph is computed. Finally, we present Potential Energy-Mutual Information based similarity metric which helps in prediction of potential links. To evaluate the performance of the proposed algorithm four similarity metrics, namely AUC, Precision, Prediction-power and Precision@K were calculated and compared with eleven baseline algorithms. The Experimental results show that the proposed method outperforms the baseline algorithms.
An efficient machine learning-based approach for screening individuals at risk of hereditary haemochromatosis
Authors: Martins Conde Patricia , Sauter Thomas , Nguyen Thanh-Phuong 
Published: November 2020

AbstractHereditary haemochromatosis (HH) is an autosomal recessive disease, where HFE C282Y homozygosity accounts for 80–85% of clinical cases among the Caucasian population. HH is characterised by the accumulation of iron, which, if untreated, can lead to the development of liver cirrhosis and liver cancer. Since iron overload is preventable and treatable if diagnosed early, high-risk individuals can be identified through effective screening employing artificial intelligence-based approaches. However, such tools expose novel challenges associated with the handling and integration of large heterogeneous datasets. We have developed an efficient computational model to screen individuals for HH using the family study data of the Hemochromatosis and Iron Overload Screening (HEIRS) cohort. This dataset, consisting of 254 cases and 701 controls, contains variables extracted from questionnaires and laboratory blood tests. The final model was trained on an extreme gradient boosting classifier using the most relevant risk factors: HFE C282Y homozygosity, age, mean corpuscular volume, iron level, serum ferritin level, transferrin saturation, and unsaturated iron-binding capacity. Hyperparameter optimisation was carried out with multiple runs, resulting in 0.94 ± 0.02 area under the receiving operating characteristic curve (AUCROC) for tenfold stratified cross-validation, demonstrating its outperformance when compared to the iron overload screening (IRON) tool.
Molecular cloning and expression analysis of sucrose phosphate synthase genes in cassava (Manihot esculenta Crantz)
Authors: Huang Tangwei , Luo Xinglu , Wei Maogui , Shan Zhongying , Zhu Yanmei , Yang Yanni , Fan Zhupeng 
Published: November 2020

AbstractSucrose phosphate synthase (SPS), a key rate-limiting enzyme in the sucrose biosynthesis pathway in plants, is encoded by a multi-gene family. Until recently, the identification and characterization of the SPS gene family have been performed for dozens of plant species; however, few studies have involved a comprehensive analysis of the SPS family members in tropical crops, such as cassava (Manihot esculenta Crantz). In the current study, five SPS genes (MeSPS1, MeSPS2, MeSPS3, MeSPS4, and MeSPS5) were isolated from cassava, and their sequence characteristics were comprehensively characterized. These MeSPS genes were found distributed on five chromosomes (Chr2, Chr14, Chr15, Chr16, and Chr18). Phylogenetic analysis showed that the MeSPS protein sequences were clustered into three families, together with other SPS sequences from both dicot and monocot species (families A, B, and C). The spatio-temporal expression pattern analysis of MeSPS genes showed a tissue-specific and partially overlapping expression pattern, with the genes mainly expressed in source tissues during cassava growth and development. Correlation analysis revealed that the expression of MeSPS genes correlated positively with root starch content, indicating that the expression of MeSPS genes might accelerate the rate of starch accumulation in the roots of cassava plants.
Characterization and classification of Romanian acacia honey based on its physicochemical parameters and chemometrics
Authors: Crăciun Mihaela Emanuela , Pârvulescu Oana Cristina , Donise Andreea Cristina , Dobre Tănase , Stanciu Dumitru Radu 
Published: November 2020

AbstractThree groups of Romanian acacia honey, i.e., pure, directly adulterated (by mixing the pure honey with three sugar syrups), and indirectly adulterated (by feeding the bees with the same syrups), were characterized and discriminated based on their physicochemical parameters. Moisture, ash, 5-hydroxymethylfurfural (HMF), reducing sugars (fructose and glucose), and sucrose contents, free acidity, diastase activity, ratio between stable carbon isotopes of honey and its proteins (δ13CH and δ13CP) were evaluated. Adulteration led to a significant increase in sucrose content, HMF level, and Δδ13C = δ13CH‒δ13CP as well a decrease in reducing sugar content and diastase activity. Principal component analysis (PCA) and linear discriminant analysis (LDA) were applied to experimental data in order to distinguish between pure and adulterated honey. The most relevant discriminative parameters were diastase activity, HMF, sucrose, and reducing sugar contents. Posterior classification probabilities and classification functions obtained by LDA revealed that 100% of honey samples were correctly assigned to their original group.
Association between the severity of hearing loss and the risk of dementia within the 2010–2017 national insurance service survey in South Korea
Authors: Chang Young-Soo , Rah Yoon Chan , Lee Min Kyu , Park Seongbin , Kim Bongseong , Han Kyungdo , Choi June 
Published: November 2020

AbstractHearing loss and dementia are highly prevalent neurologic conditions in older adults that can considerably impact the quality of life and create social and familial burdens. To investigate the impact of hearing loss on the risk of developing dementia in a nationwide long-term follow-up study using data obtained from the South Korean National Health Information Database. Retrospective medical data for patients of all ages were extracted from the database between January 2010 and December 2017. According to the national disability registry, the degree of severe-profound hearing loss is classified into six grades. We categorized hearing loss into three groups based on the disability registry severity: (1) severe hearing disability (HD), defined as 1st to 3rd grade disabling hearing loss; (2) non-severe HD, 4th and 5th grade disabling hearing loss; and (3) ipsilateral HD, 6th grade disabling hearing loss. After adjusting for potential confounding variables, the hazard ratio (HR) for all dementia types was 1.336 (95% CI 1.306–1.367) in the severe HD group, 1.312 (95% CI 1.286–1.338) in the non-severe HD group, and 1.257 (95% CI 1.217–1.299) in the ipsilateral HD group. On assessing by the age group, the risk of all dementia types in patients younger than 65 years was as follows: HR 1.933 (95% CI 1.779–2.101), 1.880 (95% CI 1.732–2.041), and 1.601 (95% CI 1.435–1.787) in the severe, non-severe, and ipsilateral HD groups, respectively. This study demonstrates that the impact of hearing loss on dementia incidence is severity-dependent, and the risk increases in patients younger than 65 years of age.
Ischial tuberosity: new donor site for bone grafts in animal cleft research
Authors: Möhlhenrich Stephan Christian , Kniha Kristian , Magnuska Zuzanna , Gremse Felix , Peters Florian , Danesh Gholamreza , Hölzle Frank , Modabber Ali 
Published: November 2020

AbstractIn the context of cleft repair in animal research in rat models, different areas can be used for bone grafting. The aim of the present study was to present the tuberosity of the ischium as a new donor site and to evaluate its quality in relation to an artificial alveolar cleft. Four weeks after creating experimental alveolar clefts in seven Wistar rats, the repair was performed in the now twelve-week-old male animals using bone blocks grafted from the ischial tuberosity. Two days before surgery and two as well as twenty-eight days after surgery, microCT scans were performed, and the grafted bone blocks were analyzed regarding height, width, thickness, and volume. Additionally, bone mineral density (BMD) and bone volume fraction (BV/TV) were measured in the repaired cleft. The mean bone volume of the graft was about 19.77 ± 7.77mm3. Immediately after jaw reconstruction the BMD and BV/TV were about 0.54 ± 0.05 g/cm3 and 54.9 ± 5.07% for the transplant and about 1.13 ± 0.08 g/cm3 and 94.5 ± 3.70%, respectively, for the surrounding bone. Four weeks later the BMD and BV/TV were about 0.57 ± 0.13 g/cm3 and 56.60 ± 13.70% for the transplant and about 11.17 ± 0.07 g/cm3 and 97.50 ± 2.15%, respectively, for the surrounding bone. A hip fracture was found in four of the animals after surgery. The ischial tuberosity offers large bone blocks, which are sufficient for cleft repair in the rat model. However, the bone quality regarding BMD and BV/TV is less compared with the surrounding bone of the alveolar cleft, even after a period of 4 weeks, despite recognizable renovation processes.
Determination of Contours of Flooded Areas Due to Possible Accident of Zhinvali (Georgia) Earth Dam and Calculation of the Hydrodynamic Parameters of a Destructive Wave at a Dam
Authors: Gavardashvili Givi , Supatashvili Tamriko , Kukhalashvili Edward , Natroshvili George , Qufarashvili Irma , Iremashvili Inga , Bziava Konstantin 
Published: November 2020

Using theoretical and field studies, computer software programs (VOLNA-4, and MIKE-21, ) and GIS technology, and taking into account the possible accident (destruction) of the Earth Dam with a height of 102 meters, the contours of the riverbed of flooded territories in riverbeds for rivers Aragvi and Mtkvari have been defined in the given article considering the configuration of the water-catchment basins of rivers.
By means of basic differential equations of hydraulics, geometrical dimensions of Zhinvali Earth Dam, hydrological basic parameters of the reservoir, and computer software, the basic hydrodynamic parameters of the destructive wave at the Zhinvali Earth Dam are calculated taking into account the time of flow movement.
Standard Changing News Onkologie in der Tumorchirurgie
Authors: Königsrainer Alfred 
Published: November 2020

ZUSAMMENFASSUNGIm Jahr 2020 haben sich bislang durch die Pandemie viele Veränderungen ergeben und die Gesamtheit der Veränderungen sind noch nicht absehbar, dies nicht nur wegen der öffentlichen Beschränkungen sondern vielmehr wegen der vielschichtigen Einflüsse auf den klinischen Alltag aller Patienten und der onkologischen Versorgung im Besonderen. Die Ergebnisse einer internationalen Datenanalyse zeigen auf, dass im Zeitraum der ersten COVID-19-Welle innerhalb von 9 Wochen weltweit ca. 28 Millionen Eingriffe abgesagt oder verschoben werden mussten 1. Für Deutschland lag die Schätzung bei 900 000 abgesagten oder verschobenen Operationen im gleichen Zeitraum. Dies betraf auch onkologische Operationen, wie ganz rezent in einer Analyse aus Abrechnungsdaten im Deutschen Ärzteblatt vom 6. Juli 2020 aufgezeigt wird 2. Das internationale Konsortium, an dem der Autor dieses Beitrages auch beteiligt ist, untersucht des Weiteren die postoperative Komplikationsrate und die perioperative Mortalität bei SARS-CoV-2-infizierten Patienten 3, aber auch die Einflüsse der Pandemie auf die chirurgische Versorgung von Tumorpatienten (Manuskript im Begutachtungsverfahren). Das erschreckend hohe perioperative Risiko, gerade nach größeren Eingriffen mit einer Pneumonierate von nahezu 50 % und einem Risiko von über 20 % innerhalb von 30 Tagen postoperativ zu versterben, erfordern umfassende Maßnahmen sowie eine Triagierung nahezu aller Tumorpatienten 4. Was dies für unsere Patienten im Einzelnen bedeutet, wird sich erst in den kommenden Monaten/Jahren zeigen.Der Jahresbeitrag beschäftigt sich in diesem Jahr ausschließlich mit dem Pankreaskarzinom und neuen Strategien in der Chirurgie sowie der perioperativen multimodalen Therapie. Zuletzt wird es noch Hinweise zum Management von Vorläuferläsionen wie intraduktaler papillär-muzinöser Neoplasien des Seitengangs (Seitengang-IPMN) geben.
Sitagliptin as an Initial Therapy and Differential Regulations of
Metabolic Parameters Depending on its Glycemic Response in Subjects with Type 2
Diabetes
Authors: Kutoh Eiji , Kuto Alexandra N. , Wada Askuka , Hayashi Jyunka , Kurihara Rumi 
Published: November 2020

AbstractThe aim of this study is to investigate whether sitagliptin can be used as an
initial drug for T2DM and to evaluate its effects on metabolic parameters in
relation to its glycemic efficacies. The subjects received
25−50 mg/day sitagliptin monotherapy (n=69).
At 3 months, they were divided into three groups (n=23 each)
according to the novel parameter called “A1c index” which is
designed to assess glycemic efficacy. The metabolic parameters were compared
between good-responders and poor-responders. These two groups acted as a
control each other. In the overall subjects, efficient reductions of HbA1c
(10.16–8.22%) were observed with few adverse events.
Significant correlations were seen between the A1c index and changes of
(∆)nonHDL-C (R=0.250) or ∆LDL-C (R=0.368).
At baseline, T-C, nonHDL-C and BMI levels were significantly lower in
good-responders than poor-responders. At 3 months, in good-responders, HbA1c
levels effectively decreased (11.03–7.00%). Indexes for
insulin sensitivity/resistance [HOMA-R and 20/(C-peptide x
FBG)] and beta-cell function (HOMA-B and CPR-index) ameliorated. T-C,
nonHDL-C and LDL-C significantly decreased, while BMI increased. However, in
poor-responders, no changes in these parameters were noted. Collectively,
these results suggest that 1) Sitagliptin can be used as a first-line drug
for T2DM and its glycemic efficacy is linked to some atherogenic lipids. 2)
Those with lower T-C, nonHDL-C and BMI appear to respond better with this
drug. 3) Good glycemic efficacy of sitagliptin is medicated through reduced
insulin resistance as well as enhanced beta-cell functions. Body weight
increased, while some atherogenic cholesterol decreased in
good-responders.