bluuebunny/crossref_metadata_2025_split huggingface dataset:
S100A8 transported by SEC23A inhibits metastatic colonization via autocrine activation of autophagy
Authors: Sun Zhiwei , Zeng Bin , Liu Doudou , Zhao Qiting , Wang Jianyu , Rosie Xing H. 
Published: August 2020

AbstractMetastasis is the main cause of failure of cancer treatment. Metastatic colonization is regarded the most rate-limiting step of metastasis and is subjected to regulation by a plethora of biological factors and processes. On one hand, regulation of metastatic colonization by autophagy appears to be stage- and context-dependent, whereas mechanistic characterization remains elusive. On the other hand, interactions between the tumor cells and their microenvironment in metastasis have long been appreciated, whether the secretome of tumor cells can effectively reshape the tumor microenvironment has not been elucidated mechanistically. In the present study, we have identified “SEC23A-S1008-BECLIN1-autophagy axis” in the autophagic regulation of metastatic colonization step, a mechanism that tumor cells can exploit autophagy to exert self-restrain for clonogenic proliferation before the favorable tumor microenvironment is established. Specifically, we employed a paired lung-derived oligometastatic cell line (OL) and the homologous polymetastatic cell line (POL) from human melanoma cell line M14 that differ in colonization efficiency. We show that S100A8 transported by SEC23A inhibits metastatic colonization via autocrine activation of autophagy. Furthermore, we verified the clinical relevance of our experimental findings by bioinformatics analysis of the expression of Sec23a and S100A8 and the clinical-pathological associations. We demonstrate that higher Sec23a and Atg5 expression levels appear to be protective factors and favorable diagnostic (TNM staging) and prognostic (overall survival) markers for skin cutaneous melanoma (SKCM) and colon adenocarcinoma (COAD) patients. And we confirm the bioinformatics analysis results with SKCM biopsy samples.
DNER promotes epithelial–mesenchymal transition and prevents chemosensitivity through the Wnt/β-catenin pathway in breast cancer
Authors: Wang Zhong , Li Zhiyu , Wu Qi , Li Chenyuan , Li Juanjuan , Zhang Yimin , Wang Changhua , Sun Si , Sun Shengrong 
Published: August 2020

AbstractBreast cancer (BC) is the most common malignant tumour in women worldwide, and one of the most common fatal tumours in women. Delta/Notch-like epidermal growth factor (EGF)-related receptor (DNER) is a transmembrane protein involved in the development of tumours. The role and potential mechanism of DNER in epithelial–mesenchymal transition (EMT) and apoptosis in BC are not fully understood. We find that DNER is overexpressed in BC tissue, especially triple-negative breast cancer (TNBC) tissue, and related to the survival of BC and TNBC patients. In addition, DNER regulates cell EMT to enhance the proliferation and metastasis of BC cells via the Wnt/β-catenin pathway in vitro and in vivo. Moreover, the expression levels of β-catenin and DNER in BD tissue are positively correlated. The simultaneously high expression of DNER and β-catenin contributes to poor prognosis in BC patients. Finally, DNER protects BC cells from epirubicin-induced growth inhibition and apoptosis via the Wnt/β-catenin pathway. In conclusion, these results suggest that DNER induces EMT and prevents apoptosis by the Wnt/β-catenin pathway, ultimately promoting the malignant progression of BC. In conclusion, our study demonstrates that DNER functions as an oncogene and potentially valuable therapeutic target for BC.
Inside the hypoxic tumour: reprogramming of the DDR and radioresistance
Authors: Begg Katheryn , Tavassoli Mahvash 
Published: August 2020

AbstractThe hypoxic tumour is a chaotic landscape of struggle and adaption. Against the adversity of oxygen starvation, hypoxic cancer cells initiate a reprogramming of transcriptional activities, allowing for survival, metastasis and treatment failure. This makes hypoxia a crucial feature of aggressive tumours. Its importance, to cancer and other diseases, was recognised by the award of the 2019 Nobel Prize in Physiology or Medicine for research contributing to our understanding of the cellular response to oxygen deprivation. For cancers with limited treatment options, for example those that rely heavily on radiotherapy, the results of hypoxic adaption are particularly restrictive to treatment success. A fundamental aspect of this hypoxic reprogramming with direct relevance to radioresistance, is the alteration to the DNA damage response, a complex set of intermingling processes that guide the cell (for good or for bad) towards DNA repair or cell death. These alterations, compounded by the fact that oxygen is required to induce damage to DNA during radiotherapy, means that hypoxia represents a persistent obstacle in the treatment of many solid tumours. Considerable research has been done to reverse, correct or diminish hypoxia’s power over successful treatment. Though many clinical trials have been performed or are ongoing, particularly in the context of imaging studies and biomarker discovery, this research has yet to inform clinical practice. Indeed, the only hypoxia intervention incorporated into standard of care is the use of the hypoxia-activated prodrug Nimorazole, for head and neck cancer patients in Denmark. Decades of research have allowed us to build a picture of the shift in the DNA repair capabilities of hypoxic cancer cells. A literature consensus tells us that key signal transducers of this response are upregulated, where repair proteins are downregulated. However, a complete understanding of how these alterations lead to radioresistance is yet to come.
The Nutrition and Health in Southwest China (NHSC) study: design, implementation, and major findings
Authors: Zhang Xiao , Chen Mengxue , Duan Ruonan , Xue Hongmei , Luo Jiao , Lv Xiaohua , Jia Hong , He Fang , Zhang Lishi , Cheng Guo 
Published: August 2020

Abstract
Background
There are few studies of nutritional and genetic factors and their interactions on the risk of noncommunicable diseases (NCDs) among Chinese adults.

Objective
Our aim for the Nutrition and Health in Southwest China (NHSC) study is to investigate the impact of diet, lifestyle, genetic background, and their interactions on NCDs among adults in Southwest China.

Methods
The NSHC is a prospective cohort study initiated in winter 2013. The baseline data collection was completed in December 2018, and follow-ups are conducted every 2 years. Information on genomics, anthropometry, nutrition, eating behaviors, physical activity, depression and mental disorders, clinical and biochemical examinations, and lifestyles was collected.

Results
7926 adults completed the baseline questionnaire. The average age of participants was 42.6 (9.8) years at study enrollment. More than half were female, 37.2% had achieved more than 12 years of education, and 49.3% of them came from family income >35,000 Yuan. Our analyses of the baseline data suggested that adults with greater dietary energy density appeared to have greater body mass index, fat mass index, fat-free mass index and percentage body fat, and that participants with a higher level of dietary glycemic index, glycemic load, or serum 25(OH)D had a less favorable glucose homeostasis. In addition, spending less time watching television and having a healthy eating pattern may play significant roles in later cellular aging.

Conclusions
In conclusion, the NHSC cohort provides valuable data for investigations of the relevance of gene, nutrition, lifestyles, and their interactions on NCDs among southwestern Chinese adults.
Development of a species-specific transformation system using the novel endogenous promoter calreticulin from oleaginous microalgae Ettlia sp.
Authors: Lee Jun-Woo , Lee Min-Woo , Ha Ji-San , Kim Dae-Soo , Jin EonSeon , Lee Hyung-Gwan , Oh Hee-Mock 
Published: August 2020

AbstractMicroalgae not only serve as raw materials for biofuel but also have uses in the food, pharmaceutical, and cosmetic industries. However, regulated gene expression in microalgae has only been achieved in a few strains due to the lack of genome information and unstable transformation. This study developed a species-specific transformation system for an oleaginous microalga, Ettlia sp. YC001, using electroporation. The electroporation was optimized using three parameters (waveform, field strength, and number of pulses), and the final selection was a 5 kV cm−1 field strength using an exponential decay wave with one pulse. A new strong endogenous promoter CRT (Pcrt) was identified using transcriptome and quantitative PCR analysis of highly expressed genes during the late exponential growth phase. The activities of this promoter were characterized using a codon optimized cyan fluorescent protein (CFP) as a reporter. The expression of CFP was similar under Pcrt and under the constitutive promoter psaD (PpsaD). The developed transformation system using electroporation with the endogenous promoter is simple to prepare, is easy to operate with high repetition, and utilizes a species-specific vector for high expression. This system could be used not only in molecular studies on microalgae but also in various industrial applications of microalgae.
Tumoral and paratumoral NK cells and CD8+ T cells of esophageal carcinoma patients express high levels of CD47
Authors: Strizova Zuzana , Vachtenheim Jiri , Snajdauf Martin , Lischke Robert , Bartunkova Jirina , Smrz Daniel 
Published: August 2020

AbstractIn a limited number of human malignancies, anti-CD47 therapy leads to the rapid clearance of tumor cells by macrophages. In esophageal squamous cell carcinoma, anti-CD47 treatment has shown promising results in vitro. However, the CD47 expression pattern in tumor-infiltrating lymphocytes (TILs), which are associated with prolonged overall survival and serve as a positive prognostic factor, is largely unknown. In this study, a total of 36 tissue samples from the tumor, peritumoral tissue, and adjacent healthy esophageal tissue was obtained from 12 esophageal carcinoma (EC) patients, and the surface expression of CD47 was evaluated in natural killer (NK) cells, CD8+ T cells, and the nonlymphocyte cell fraction. We found that the proportions of the evaluated cells and their CD47-expressing populations were comparable across the analyzed tissue compartments. However, the proportions of CD47-expressing populations in the analyzed tissue compartments were significantly higher in NK cells and CD8+ T cells than in the nonlymphocyte cell fraction. Importantly, the intensity of CD47 staining was also significantly higher in the tested immune cells than in the nonlymphocyte cell fraction. High expression of CD47 in tissue-infiltrating NK cells and CD8+ T cells in EC patients can, therefore, affect the efficacy of anti-CD47 therapy in EC.
Multicoding in neural information transfer suggested by mathematical analysis of the frequency-dependent synaptic plasticity in vivo
Authors: Hata Katsuhiko , Araki Osamu , Yokoi Osamu , Kusakabe Tatsumi , Yamamoto Yoshio , Ito Susumu , Nikuni Tetsuro 
Published: August 2020

AbstractTwo elements of neural information processing have primarily been proposed: firing rate and spike timing of neurons. In the case of synaptic plasticity, although spike-timing-dependent plasticity (STDP) depending on presynaptic and postsynaptic spike times had been considered the most common rule, recent studies have shown the inhibitory nature of the brain in vivo for precise spike timing, which is key to the STDP. Thus, the importance of the firing frequency in synaptic plasticity in vivo has been recognized again. However, little is understood about how the frequency-dependent synaptic plasticity (FDP) is regulated in vivo. Here, we focused on the presynaptic input pattern, the intracellular calcium decay time constants, and the background synaptic activity, which vary depending on neuron types and the anatomical and physiological environment in the brain. By analyzing a calcium-based model, we found that the synaptic weight differs depending on these factors characteristic in vivo, even if neurons receive the same input rate. This finding suggests the involvement of multifaceted factors other than input frequency in FDP and even neural coding in vivo.
Neutrophil extracellular trap from Kawasaki disease alter the biologic responses of PBMC
Authors: Jing Yang , Ding Meng , Fu Jiuyuan , Xiao Yanping , Chen Xianghua , Zhang Qingyun 
Published: August 2020

AbstractKawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute systemic vasculitis syndrome that mainly occurs in infants under 5 years of age. In the current manuscript, we were aiming to analyze the role of neutrophil extracellular traps (NETs) in the pathogenesis of KD, especially their interplay with peripheral blood mononuclear cells (PBMCs). Neutrophils were exposed to 20 nM phorbol myristate acetate (PMA), we found that neutrophils of KD patients were more likely to form NETs compared with healthy controls (HCs). Furthermore, PBMCs were cultured with NETs for 24 h, and we observed that NETs significantly increased the cell viability, suppressed cell apoptosis, and enhanced the pro-inflammatory cytokines production and NF-κB activation in PBMCs from KD patients. In addition, with the stimulation of NETs, the expression of vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) were increased, which were related with the pathological mechanism of KD. At last, we examined the activation of phosphoinositide 3 kinase (PI3K)/Akt signaling, and we found NETs treatment obviously enhanced the activation of PI3K and Akt. In conclusion, these findings suggested that the formation of NETs may alter the biologic responses of PBMC and affect the vascular injury in KD.
Joint Attention and Sensory-Regulatory Features at 13 and 22 Months as Predictors of Preschool Language and Social-Communication Outcomes
Authors: Nowell Sallie W. , Watson Linda R. , Crais Elizabeth R. , Baranek Grace T. , Faldowski Richard A. , Turner-Brown Lauren 
Published: August 2020

PurposeThe purpose of this study was to understand how joint attention and sensory-regulatory features are related in early childhood and predict language and social-communication outcomes in preschool in order to build mechanistic theories that can inform early intervention directed at improving these outcomes.MethodCross-lagged panel analysis models were used to examine the association between joint attention and sensory-regulatory features at 13 and 22 months of age in children (n= 87) who were identified via community screening at 12 months as having a higher likelihood than the general population for being diagnosed with autism spectrum disorder.ResultsSignificant concurrent correlations and predictive correlations were found between these constructs at 13 and 22 months. Joint attention skills at 13 months predicted both joint attention and sensory-regulatory features at 22 months. Distal language and social-communication outcomes at preschool age (n= 48) were best predicted by sensory-regulatory features at 22 months.ConclusionsBoth joint attention and sensory regulation are important factors in the first and second years of life for impacting later preschool language and social-communication outcomes in this sample. These findings may have implications for future early childhood intervention research for children at a higher likelihood for autism spectrum disorder.
1V relaxation oscillator with integrated voltage and current reference
Authors: Wang Lidan , Zhan Chenchang 
Published: August 2020

This Letter presents a novel relaxation oscillator with integrated voltage and current reference circuit, which generates a 32 kHz clock reference with 1% accuracy and has total power consumption of 122 nW at 1 V. Its temperature coefficient (TC) is 104 ppm/°C with a temperature range of −40 to 100°C, and its supply voltage accuracy is 1.6%/V from 1 to 1.8 V. The proposed oscillator uses the voltage reference directly to compare with the charging capacitor voltage, and the charging current is derived from the voltage reference divided by one temperature‐independent resistor. The advantages are that the accuracy of output frequency and TC can be trimmed simultaneously and independently. It is fabricated in 0.18 μm CMOS technology and occupies 0.059 mm2 including the voltage and current reference circuits.
Dehydratation verstehen – wie viel Wasser braucht der ältere Mensch?
Authors: Wirth Rainer 
Published: August 2020

ZusammenfassungAls Exsikkose oder auch Dehydratation bezeichnet man ganz allgemein eine Symptomatik, die auf einen unphysiologisch niedrigen Wassergehalt des Organismus zurückzuführen ist. Aufgrund vieler im Alter häufigen Erkrankungen, aber auch vor dem Hintergrund des im Alter oft nachlassenden Durstgefühls, sind ältere Menschen besonders gefährdet, eine Dehydratation zu entwickeln. Die Symptomatik der Dehydratation geht nicht nur mit Schwäche und ggf. Verwirrtheit einher, sondern kann zu vielen Sekundärerkrankungen führen. Beispielsweise ist das Orthostasesyndrom, welches gehäuft zu Stürzen und Frakturen führt, meist durch eine Dehydratation bedingt. Die Diagnosestellung der Dehydratation ist gelegentlich schwierig, da keines der diagnostischen Zeichen über eine ausreichende Sensitivität und Spezifität verfügt. So kann die Diagnose meist nur aus der Gesamtschau des Patienten gestellt werden und durch eine erfolgreiche Therapie bestätigt werden. Für eine wirksame Prävention ist eine ausreichende tägliche Flüssigkeitszufuhr unumgänglich. Die 2018 veröffentlichte ESPEN-Leitlinie zur Klinischen Ernährung und Flüssigkeitsversorgung geriatrischer Patienten empfiehlt die Zufuhr von 1,6 und 2,0 Liter Getränken pro Tag für ältere Frauen und Männer.
Mikronährstoffdosierungen in Nahrungsergänzungsmitteln im Vergleich zu den Höchstmengenvorschlägen des Bundesinstituts für Risikobewertung
Authors: von Lippe Maximilian , Mosler Stephanie , Lührmann Petra , Carlsohn Anja 
Published: August 2020

Zusammenfassung
Hintergrund Das Bundesinstitut für Risikobewertung (BfR) veröffentlichte im Januar 2018 Höchstmengenvorschläge (HMV) für Vitamine und Mineralstoffe in Nahrungsergänzungsmitteln (NEM). Die vorliegende Arbeit untersucht beispielhaft die Einhaltung der HMV in NEM aus dem Einzelhandel.
Material und Methodik In dieser Pilotstudie im Querschnittdesign wurden 106 NEM aus einem Reformhaus, einem Supermarkt und 2 Drogerien aus Schwäbisch Gmünd hinsichtlich ihrer Mikronährstoffdosierungen untersucht. Für die Analysen wurden die Nährstoffangaben auf den Verpackungen der einzelnen Präparate herangezogen, in einer Datenbank erfasst und mit den jeweiligen HMV für Vitamine und Mineralstoffe in NEM verglichen.
Ergebnisse Insgesamt wurden 30 Einzelvitaminpräparate, 11 Einzelmineralstoffpräparate, 44 Multivitaminpräparate, 11 Multimineralpräparate und 10 Multivitamin- und Multimineralstoffpräparate untersucht. Von den 106 untersuchten NEM hielten ca. 48 % die HMV bei allen Nährstoffen ein. Eine Überschreitung der HMV bei mindestens einem Mikronährstoff wiesen 55 Präparate (51,8 %) auf. Die HMV wurden am häufigsten bei Multivitamin- und Multimineralstoffpräparaten (80 % der Präparate) überschritten.
Schlussfolgerung Die Untersuchung zeigt, dass mehr als die Hälfte der untersuchten NEM aus dem stationären Einzelhandel in Schwäbisch Gmünd die HMV des BfR für Vitamine und Mineralstoffe überschreiten. Das ist bedenklich, da mit dem Gebrauch von hoch dosierten Vitamin- und Mineralstoffpräparaten gesundheitliche Risiken einhergehen können, insbesondere bei hoher habitueller Zufuhr. VerbraucherInnen sollten somit auf die möglichen Risiken, die aus der Einnahme von NEM resultieren können, hingewiesen werden. Verbindliche Höchstmengen sowie EU-weite einheitliche Richtlinien für Mikronährstoff-Höchstmengen in NEM wären möglicherweise sinnvoll.
Sleepiness, sleep duration, and human social activity: An investigation into bidirectionality using longitudinal time-use data
Authors: Holding Benjamin C. , Sundelin Tina , Schiller Helena , Åkerstedt Torbjörn , Kecklund Göran , Axelsson John 
Published: August 2020

Significance
We observe that a change from very alert to very sleepy can decrease social contact by approximately 70%. We also reveal moderators of this effect, such as time of day. This finding provides a perspective on, and possible mechanism as to, why sleep disturbances and other causes of sleepiness (such as medicine side effects or shift work), are associated with poorer health outcomes. It is especially urgent to understand the causes of decreased social activity, as rates of social isolation and loneliness are reported to be rising, as are rates of sleep disturbance. The results provide directions for future research, for example regarding whether interventions to alleviate sleepiness can be an effective way to improve both short- and long-term well-being.
The formation of trapped surfaces in the gravitational collapse of spherically symmetric scalar fields with a positive cosmological constant
Authors: Costa João L 
Published: August 2020

Abstract
Given spherically symmetric characteristic initial data for the Einstein-scalar field system with a positive cosmological constant, we provide a criterion, in terms of the dimensionless size and dimensionless renormalized mass content of an annular region of the data, for the formation of a future trapped surface. This corresponds to an extension of Christodoulou’s classical criterion by the inclusion of the cosmological term.
A novel method for impact force estimation in composite plates under simulated environmental and operational conditions
Authors: Seno Aldyandra Hami , Aliabadi M H Ferri 
Published: August 2020

Abstract
During its lifetime, an aircraft structure is subjected to various impacts from various sources such as tool drops, hail, ground service equipment, etc. In modern composite structures, these impacts have a significant chance of generating barely visible damage (BVID) which may lead to catastrophic failure of a structure if left undetected to grow. However, BVID is difficult to detect during routine visual inspection without specialised non-destructive inspection and thus there is large interest in developing monitoring systems for estimating the location and severity of impact events. Currently, most systems and methods have been developed for controlled lab conditions and do not consider the wide range of impact parameters in real life operation (environmental conditions, vibration, impactor stiffness, angle, etc) which may severely compromise the accuracy of these methods. In this study we have explored two methods for maximum impact force estimation, deconvolution and a novel gradient method, for the purpose of reliable severity assessment in composite aircraft structures under simulated environmental and operational conditions. It is shown that both methods allow accurate and robust estimation of the maximum impact force from various cases of impacts (variation of impact energy, mass, stiffness, angle, temperature, source) using minimum initial data from a single impact case. From further testing it is demonstrated that the gradient method is robust towards the effects of impact localisation errors and noise. The gradient method also has much less computational and storage requirements and is thus more feasible to integrate with current data acquisition systems being developed for structural health monitoring. Thus, we conclude that the proposed gradient method is suitable for impact force monitoring and severity assessment in composite aircraft structures in the simulated environmental and operational conditions.