bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing Two-Echelon Remanufacturing Under Patent Protection
Authors: Cao Xiaogang , Wen Hui 
Published: February 2021

Abstract
We propose a two-echelon remanufacturing model in the context of two periods in which the factor of patent protection of the original manufacturer is considered. Through the analysis of the Stackelberg game among the supplier, the original manufacturer and the remanufacturer we obtain the equilibrium solutions of the unit patent licensing fee of the original manufacturer, the recycling effort degree of the remanufacturer, the wholesale price of new and remanufactured core components and the retail price of new and remanufactured products in the second period which are all dependent on the retail price of new products in the first period in cases with patent protection and without patent protection. In the numerical study we analyze the impacts of the remanufacturing rate of used products and the retail price of new products in the first period on the equilibrium results of the second period, and make a comparison between the case with patent protection and the case without patent protection.
Load Balancing Algorithm of Controller Based on SDN Architecture Under Machine Learning
Authors: Liang Siyuan , Jiang Wenli , Zhao Fangli , Zhao Feng 
Published: February 2021

Abstract
With the rapid development of cloud computing and other related services, higher requirements are put forward for network transmission and delay. Due to the inherent distributed characteristics of traditional networks, machine learning technology is difficult to be applied and deployed in network control. The emergence of SDN technology provides new opportunities and challenges for the application of machine learning technology in network management. A load balancing algorithm of Internet of things controller based on data center SDN architecture is proposed. The Bayesian network is used to predict the degree of load congestion, combining reinforcement learning algorithm to make optimal action decision, self-adjusting parameter weight to adjust the controller load congestion, to achieve load balance, improve network security and stability.
Monolayer platform to generate and purify human primordial germ cells in vitro provides new insights into germline specification
Authors: Sebastiano Vittorio , Kang Gugene , Vijayakumar Sivakamasundari , Sala Roberta , Chen Angela , Adebayo Abidemi , Cipriano Andrea , Fowler Jonas , Ang Lay Teng , Loh Kyle 
Published: February 2021

Abstract
Generating primordial germ cells (PGCs) from human pluripotent stem cells (hPSCs) advances studies of human reproduction and development of infertility treatments, but currently entails complex 3D aggregates. Here we develop a simplified, monolayer method to differentiate hPSCs into PGCs within 3.5 days. We used our simplified differentiation platform and single-cell RNA-sequencing to uncover new insights into PGC specification. Transient WNT activation for 12 hours followed by WNT inhibition specified PGCs; by contrast, sustained WNT instead induced primitive streak. Thus, somatic (primitive streak) and PGCs are related—yet distinct—lineages segregated by temporally-dynamic signaling. Pluripotency factors including NANOG are continuously expressed during the transition from pluripotency to posterior epiblast to PGCs, thus bridging pluripotent and germline states. Finally, hPSC-derived PGCs can be easily purified by virtue of their CXCR4+PDGFRA−GARP− surface-marker profile and single-cell RNA-sequencing reveals that they harbor strong transcriptional similarities with fetal PGCs.
One-pot production of butyl butyrate from glucose using a cognate “diamond-shaped” E. coli consortium
Authors: Sinumvayo Jean Paul , Zhao Chunhua , Liu Guoxia , Li Yin , Zhang Yanping 
Published: February 2021

Abstract
Esters are widely used in plastics, textile fibers, and general petrochemicals. Usually, esters are produced via chemical synthesis or enzymatic processes from the corresponding alcohols and acids. However, the fermentative production of esters from alcohols and/or acids has recently also become feasible. Here we report a cognate microbial consortium capable of producing butyl butyrate. This microbial consortium consists of two engineered butyrate- and butanol-producing E. coli strains with nearly identical genetic background. The pathways for the synthesis of butyrate and butanol from butyryl-CoA in the respective E. coli strains, together with a lipase-catalyzed esterification reaction, created a “diamond-shaped” consortium. The concentration of butyrate and butanol in the fermentation vessel could be altered by adjusting the inoculation ratios of each E. coli strain in the consortium. After optimization, the consortium produced 7.2 g/L butyl butyrate with a yield of 0.12 g/g glucose without the exogenous addition of butanol or butyrate. To our best knowledge, this is the highest titer and yield of butyl butyrate produced by E. coli reported to date. This study thus provides a new way for the biotechnological production of esters.
Steroids as the novel class of high-affinity allosteric modulators of muscarinic receptors
Authors: Dolejší Eva , Szánti-Pintér Eszter , Chetverikov Nikolai , Nelic Dominik , Randáková Alena , Doležal Vladimír , Kudová Eva , Jakubik Jan 
Published: February 2021

Abstract
The membrane cholesterol was found to bind and modulate the function of several G-protein coupled receptors including muscarinic acetylcholine receptors. We investigated the binding of 20 steroidal compounds including neurosteroids and steroid hormones to muscarinic receptors. Corticosterone, progesterone, and some neurosteroids bound to muscarinic receptors with an affinity of 100 nM or greater. We established a structure-activity relationship for steroid-based allosteric modulators of muscarinic receptors. Further, we show that corticosterone and progesterone allosterically modulate the functional response of muscarinic receptors to acetylcholine at physiologically relevant concentrations. It can play a role in stress control or in pregnancy, conditions where levels of these hormones dramatically oscillate. Allosteric modulation of muscarinic receptors via the cholesterol-binding site represents a new pharmacological approach at diseases associated with altered cholinergic signalling.
Increased Expression of eEF1A2 and PI3K-Akt Signaling Pathway Genes Promotes The Progression of Cervical Cancer
Authors: Xin Huizhen , Pan Huan , Zhe Xiangyi , Zhang Chunhe , Li Hongtao , Zheng Weinan , Shao Renfu , Li Dongmei , Pan Zemin 
Published: February 2021

Abstract
Objective: This study sought to explore the mRNA and protein expression levels of eukaryotic translation elongation factor 1 alpha 2 (eEF1A2) and members of the PI3K-Akt signaling pathway in the context of cervical cancer. We sought to clarify the expression of eEF1A2, PI3K, Akt during cervical cancer tumorigenesis and development.Methods: Samples from 72 cases of cervical cancer were collected, as well as 46 cases of cervical intraepithelial neoplasia (CIN), which reflects the continuous process of cervical cancer development, divided into CIN I, CIN II, CIN III, and 40 cases of chronic cervicitis. qRT-PCR was to detect the mRNA levels of eEF1A2, PI3K, and Akt, with β-actin used as an internal control. eEF1A2, PI3K, p-Akt protein levels in cervical cancer, CIN, and chronic cervicitis tissues were detected by immunohistochemical. eEF1A2, PI3K and p-Akt protein expression levels in HeLa, SiHa, and human umbilical vein endothelial cells were detected by western blot.Results: qRT-PCR results showed that the level of mRNA expression of eEF1A2, PI3K, and Akt was higher in cervical cancer tissues than that in normal cervical tissues. Immunohistochemistry results showed that the eEF1A2, PI3K, and p-Akt protein levels were higher in cervical cancer tissues than in cervical chronic cervicitis tissues. The differences were statistically significant (P < 0.05). The expression of eEF1A2, PI3K, and p-Akt protein was higher in HeLa and SiHa cervical cell lines than that in normal epithelial cells.Conclusion: Together, these results suggest that the aberrant expression of eEF1A2, PI3K, and Akt may play a role in cervical cancer development and tumorigenesis.
Direct ink writing of 3D thermoelectric architectures for fabrication of micro power generators
Authors: Kim Fredrick , Yang Seong Eun , Ju Hyejin , Choo Seungjun , Lee Jungsoo , Kim Gyeonghun , Jung Soo-Ho , Kim Suntae , Cha Chaenyung , Kim Kyung Tae , Ahn Sangjoon , Chae Han Gi , Son Jae Sung 
Published: February 2021

Abstract
Micro-thermoelectric modules can be used to develop unique components such as energy harvesters, active coolers, and thermal sensors in various integrated systems. However, the manufacturing of these modules still relies on costly traditional micro-fabrication processes, producing only two-dimensional (2D) thermoelectric films. This limitation severely constrains temperature gradient formation across thermoelectric films, and hence, the sufficient amount of power required to run integrated systems is not generated. Herein, we present the direct ink writing of micro-scale three-dimensional (3D) thermoelectric architectures for fabricating high-performance micro-thermoelectric generators. The characteristics of (Bi, Sb)2(Te, Se)3-based particles were precisely engineered such that the colloidal inks achieved outstanding viscoelasticity, thereby facilitating the creation of complex 3D architectures having high thermoelectric figure-of-merits of 1.1 (p-type) and 0.5 (n-type). Micro-thermoelectric generators made of 3D-written vertical filaments exhibited large temperature gradients and a good resulting power density, opening an avenue for the cost-effective and rapid manufacturing of integrated micro-thermoelectric modules.
Role of Insulin/Glucagon Ratio and Cell Redox State in the Hyperglycaemia Induced by Exposure to Electromagnetic Fields in Rats.
Authors: Martiñón-Gutiérrez Gabriel , Luna-Castro María , Hernández-Muñoz Rolando 
Published: February 2021

Abstract
The exposure to extremely low-frequency electromagnetic fields (EMFs) with a might adversely affect the endocrine system and reproductive functions. Nonetheless, the use of EMFs in the form of magneto-therapy exerts beneficial actions in human medicine, but also affecting glucose and lipids metabolism, inducing hyperglycaemia and a “diabetic” response. Therefore, we used fed or fasted male rats for a single exposure to 60-Hz EMFs, determining serum levels of glucose, lipids, and indicators of cellular redox state and energy parameters. A single exposure to EMFs induced hyperglycaemia in both, fed and fasted rats, accompanied by an attenuated second serum insulin peak. In addition, EMFs also decreased serum levels of free fatty acids and lactate, while they increased those of pyruvate and acetoacetate. Changes in blood glucose level were related with a more oxidized cellular redox state and with the insulin/glucagon ratio. Moreover, rat’s glucose metabolism also coincided with variations in insulin and glucagon secretion, probably depending on cell redox state. The EMFs effects were not modified in animals previously subjected to a chronic exposure (14 days). In conclusion, increased serum glucose levels and glucose metabolism induced by EMFs exposure were closely related with the cellular redox state and with the insulin/glucagon ratio.
Association Between Phosphate Disturbances and Mortality Among Critically Ill Patients With Sepsis or Septic Shock
Authors: Harbi Shmeylan Al , Al-Dorzi Hasan , Meshari Albatool Al , Tamim Hani , Abdukahil Sheryl Ann , Sadat Musharaf , Arabi Yaseen 
Published: February 2021

Abstract
Objective: The aim of this study is to examine the association of hypophosphatemia and hyperphosphatemia on the first day of ICU admission with mortality in septic critically ill patients. Methods: In this retrospective cohort study, all adult patients who were admitted to medical-surgical ICUs between 2014 and 2017 with sepsis or septic shock were categorized as having hypophosphatemia, hyperphosphatemia or based on day 1 serum phosphate values. We compared the clinical characteristics and outcomes between the three groups. We used multivariate analysis to examine the association of hypophosphatemia and hyperphosphatemia with these outcomes.Results: Of the 1422 patients enrolled in the study, 188 (13%) had hypophosphatemia, 865 (61%) normophosphatemia and 369 (26%) had hyperphosphatemia. Among the three groups, the patients in the hyperphosphatemia group had significantly lower GCS, higher APACHE II scores, higher serum creatinine, increased use of vasopressors, and required mechanical ventilation with lower PaO2/FiO2 ratio compared with the other two groups. In addition, hyperphosphatemia group also showed significantly higher ICU mortality and hospital mortality in comparison to the other two groups. Conclusion: Hyperphosphatemia and not hypophosphatemia on the first ICU admission day was associated with an increase in the ICU and hospital mortality in septic critically ill patients.
FABP3 deficiency exacerbates metabolic derangement in cardiac hypertrophy via PPARα pathway
Authors: Zhuang Lingfang , Liu Zizhu , Li Chenni , Jin Qi , Lu Lin , Tao Rong , Yan Xiaoxiang , Chen Kang 
Published: February 2021

Abstract
Cardiac hypertrophy was accompanied by various cardiovascular diseases (CVDs), due to the high global incidence and mortality of CVDs, it has become increasingly critical to characterize the pathogenesis of cardiac hypertrophy. We aimed to determine the metabolic effects of fatty acid binding protein 3 (FABP3), on transverse aortic constriction (TAC)-induced cardiac hypertrophy. TAC or Ang II treatment markedly upregulated Fabp3 expression. Notably, Fabp3 ablation aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction. Multi-omics analysis revealed that Fabp3-deficient hearts exhibited disrupted metabolic signatures characterized by increased glycolysis, toxic lipid accumulation, and compromised fatty acid oxidation and ATP production under hypertrophic stimuli. Mechanistically, FABP3 mediated metabolic reprogramming by directly interacting with PPARa, which stabilized and regulated its transcriptional activity on Mlycd, Gck. Finally, treatment with the PPARa agonist, fenofibrate, rescued the pro-hypertrophic effects of Fabp3 deficiency. Collectively, these findings indicate that the FABP3-PPARa axis contributes to metabolic homeostasis and participates in the development of hypertrophy and heart failure.
End-of-life Care Preferences among Cancer Patients in Southern Thailand: A University Hospital-based Cross-Sectional Survey
Authors: Pitanupong Jarurin , Janmanee Sahawit 
Published: February 2021

Abstract
Background: End-of-life care preferences may be highly individual, heterogenic, and variable according to culture and belief. This study aimed to explore preferences and factors associated with end-of-life care among Thai cancer patients with the goal of helping optimize their quality of life.Methods: A cross-sectional study surveyed cancer outpatients at Songklanagarind Hospital from August to November 2020. The questionnaires inquired about: 1) personal and demographic information, 2) experiences with end-of-life care received by relatives, and 3) end-of-life care preferences. To determine end-of life preferences, the data were analyzed using descriptive statistics. The data concerning patient demographics and end-of-life care preferences were compared using Fisher’s exact test. Results: The majority of the 96 cancer outpatients were female (65.6%), and the overall mean age was 55.8 ±11.6 years. More than half of them had an experience of observing someone die (68.8%), and they were predominantly satisfied with the care received by their relatives in passing away at home surrounded by family (47.0%) and being conscious until the time of death (68.2%). Most participants preferred receiving the full truth regarding their illness (99.0%), being free of uncomfortable symptoms (96.9%), having their loved ones around (93.8%), being mentally aware at the last hour (93.8%), and having the sense of being meaningful in life (92.7%). Their 3 most important end-of-life care wishes were receiving the full truth regarding their illness, disclosing the full truth regarding their illness to family members, and passing away at home. Conclusion: In order to optimize the quality of life of terminal patients, end-of-life care should ensure they receive the full truth regarding their illness, experience no distress symptoms, remain mentally aware at the last hour of life, feel meaningful in life, and pass away comfortably with loved ones around.
P2X7 Receptors and TMEM16 Channels Form a Hub with Implications for Macropore Formation and Current Facilitation
Authors: Dunning Kate , Martz Adeline , Peralta Francisco , Cevoli Federico , Boué-Grabot Eric , Taly Antoine , Compan Vincent , Gautherat Fanny , Wolf Patrick , Chataigneau Thierry , Grutter Thomas 
Published: February 2021

Abstract
P2X7 receptors (P2X7) are cationic channels involved in many diseases. They exhibit unique behaviors, such as “macropore” formation, which corresponds to enhanced large molecule cell membrane permeability, and current facilitation, which is caused by prolonged activation. These two phenomena have often been confounded, but thus far no clear mechanisms have been resolved. Here we provide evidence that current facilitation and macropore formation involve functional complexes comprised of P2X7 and TMEM16, a family of Ca2+-activated ion channel/scramblases. We found that current facilitation results in an increase of complex-embedded P2X7 open channel probability, a result mimicked by plasma membrane cholesterol depletion. We further show that macropore formation entails two distinct large molecule permeation components, one of which requires protein complexes featuring TMEM16F subtype, the other likely being direct permeation through the P2X7 pore itself. Such protein complexes can be considered to represent a regulatory hub intimately involved in distinct P2X7 functionalities.
Integrated Bioinformatics Analysis of Differentially-Expressed Genes and Immune Cell Infiltration Characteristics in Esophageal Squamous Cell Carcinoma
Authors: Feng Zitong , Qu Jingge , Liu Xiao , Liang Jinghui , Li Yongmeng , Jiang Jin , Zhang Huiying , Tian Hui 
Published: February 2021

Abstract
Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. Identifying the best-targeted therapy, appropriate biomarkers and individual treatment for patients with ESCC remains a significant challenge. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. We downloaded nine gene expression datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between ESCC tissues and normal tissues in each dataset were identified by the “limma” R package, and a total of 152 robust DEGs were identified by robust rank aggregation (RRA) algorithm. Functional enrichment analyses of the robust DEGs showed that these genes were significantly associated with extracellular matrix related process. Immune cell infiltration analysis was also conducted by CIBERSORT algorithm. We found that M0 and M1 macrophages were increased dramatically in ESCC while M2 macrophages decreased. Nine hub genes were picked out from a protein-protein interaction (PPI) network used by the CytoHubba plugin in Cytoscape. According to the receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis, the genes PLAU, SPP1 and VCAN had high diagnostic and prognostic values for ESCC patients. Based on univariate and multivariate regression analyses, seven genes (IL18, PLAU, ANO1, SLCO1B3, CST1, NELL2 and MAGEA11) from the robust DEGs were used to construct a good prognostic model. A nomogram that incorporates seven genes signature was established to develop a quantitative method for ESCC prognosis. Our results might provide aid for exploring potential therapeutic targets and prognosis evaluation in ESCC.
Characteristics of 1270 Chinese Sibling Pairs with Cancer
Authors: Liu Ju , Yin Jian , Liu Yiwei , Xu Zhijian , Zhang Kai 
Published: February 2021

Abstract
Background: Previous research found that the cancer history of an individual’s sibling may be a better indicator than that of the parents. We aim to provide recommendations for early screening for individuals whose sibling had been diagnosed with cancer. Methods: During the physical examination in Cancer Hospital, Chinese Academy of Medical Sciences, 43,300 people were asked if they have at least two siblings who developed cancer. Eligible participants were asked to fill out a survey and participate in interviews. Results: A total of 1270 sibling-pairs from 766 families developed cancer, including 367 pairs of brothers (Bro-pairs), 368 pairs of sisters (Sis-pairs), and 535 pairs of brother-and-sister (BroSis-pairs). The mean ages at diagnosis of cancer for the three groups were from 58 to 62 years. More than half of Bro-pairs (55.3%) or Sis-pairs (51.1%) had cancer from the same systemic origin, and more than a quarter of Bro-pairs (28.1%) and Sis-pairs (37.2%) developed the same type of cancer. However, only 36.0% of BroSis-pairs developed cancers from the same systemic origin, and 18.9% developed the same type of cancer. In Bro-pairs and BroSis-pairs, lung cancer and digestive system cancer were the most common cancers, while in Sis-pairs, breast cancer, lung cancer, cervical cancer, liver cancer and thyroid cancer the most common ones. Conclusions: If an individual’s sibling is diagnosed with cancer, the individual should be screened as soon as possible, especially for lung cancer and digestive system cancers for both sexes. For sisters, breast cancer, cervical cancer and thyroid cancer should be screened early. Additionally, genetic services are essential for individuals who have siblings with cancer.