bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards Secretome Standardization: Identifying Key Ingredients of MSC-Derived Therapeutic Cocktail
Authors: Giannasi Chiara , Niada Stefania , Della Morte Elena , Casati Sara , Orioli Marica , Gualerzi Alice , Brini Anna Teresa 
Published: August 2021

The therapeutic potential of the conditioned medium (CM) derived from MSCs (mesenchymal stem/stromal cells) in disparate medical fields, from immunology to orthopedics, has been widely suggested by in vitro and in vivo evidences. Prior to MSC-CM use in clinical applications, appropriate quality controls are needed in order to assess its reproducibility. Here, we evaluated different CM characteristics, including general features and precise protein and lipid concentrations, in 3 representative samples from adipose-derived MSCs (ASCs). In details, we first investigated the size and distribution of the contained extracellular vesicles (EVs), lipid bilayer-delimited particles whose pivotal role in intercellular communication has been extensively demonstrated. Then, we acquired Raman signatures, providing an overlook of ASC-CM composition in terms of proteins, lipids, and nucleic acids. At last, we analyzed a panel of 200 molecules including chemokines, cytokines, receptors, and inflammatory and growth factors and searched for 32 lipids involved in cell signalling and inflammation. All ASC-CM contained a homogeneous and relevant number of EVs (

1.0
×

10

9

±
1.1
×

10

8

particles per million donor ASCs) with a mean size of

190
±
5.2

nm

, suggesting the appropriateness of the method for EV retaining and concentration. Furthermore, also Raman spectra confirmed a high homogeneity among samples, allowing the visualization of specific peaks for nucleic acids, proteins, and lipids. An in depth investigation that focused on 200 proteins involved in relevant biological pathways revealed the presence in all specimens of 104 factors. Of these, 26 analytes presented a high degree of uniformity, suggesting that the samples were particularly homogenous for a quarter of the quantified molecules. At last, lipidomic analysis allowed the quantification of 7 lipids and indicated prostaglandin-E2 and N-stearoylethanolamide as the most homogenous factors. In this study, we assessed that ASC-CM samples obtained with a standardized protocol present stable features spanning from Raman fingerprint to specific marker concentrations. In conclusion, we identified key ingredients that may be involved in ASC-CM therapeutic action and whose consistent levels may represent a promising quality control in the pipeline of its preparation for clinical applications.
Quality Diet Index and Risk of Pancreatic Cancer: Findings from the Singapore Chinese Health Study
Authors: Luu Hung N. , Paragomi Pedram , Jin Aizhen , Wang Renwei , Neelakantan Nithya , van Dam Rob M. , Brand Randall E. , Koh Woon-Puay , Yuan Jian-Min 
Published: August 2021

Abstract

Background:
Limited research has been conducted on the effect of quality diet index (QDI), which represents a comprehensive assessment of healthy diet quality and quantity, on pancreatic cancer risk in Asian populations.

Methods:
Using data from the Singapore Chinese Health Study, a prospective cohort of 63,257 middle-aged or older Chinese men and women, four QDI scores: the Alternative Health Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH), and the Heathy Diet Indicator (HDI), at baseline were calculated. After 25 years of follow-up, 311 cohort participants developed pancreatic cancer. Cox proportional hazard regression method was used to estimate HR and 95% confidence interval (CI) for pancreatic cancer associated with higher QDI scores.

Results:
Higher scores of AHEI-2010, aMED, and DASH were significantly associated with lower pancreatic cancer risk (all Ptrend &lt; 0.05). Compared with the lowest quartile, HRs (95% CIs) of pancreatic cancer for the highest quartiles of AHEI-2010, aMED, and DASH scores were 0.65 (0.46–0.90), 0.57 (0.38–0.85), and 0.66 (0.46–0.95), respectively. These associations were more apparent among men. Overall, there was no statistically significant difference in the QDI–pancreatic cancer risk association between subgroups stratified by levels of body mass index, history of diabetes, and smoking status.

Conclusions:
Higher QDI scores were significantly associated with reduced risk of pancreatic cancer.

Impact:
The consistent results across multiple QDIs shows that adherence to a healthy diet may lower pancreatic cancer risk, suggesting that dietary modification may be a promising approach for primary prevention of pancreatic cancer.
Long-term Lung Cancer Risk Associated with Sputum Atypia: A 27-Year Follow-up Study of an Occupational Lung Screening Cohort in Yunnan, China
Authors: Fan Yaguang , Su Zheng , Wei Mengna , Liang Hao , Jiang Yong , Li Xuebing , Meng Zhaowei , Wang Ying , Pan Hongli , Song Jinzhao , Qiao Youlin , Zhou Qinghua 
Published: August 2021

AbstractBackground:Sputum cytologic atypia is associated with increased lung cancer risk. However, little is known about the long-term magnitude and temporal trend of this risk.Methods:An extended follow-up was conducted in a prospective screening cohort among occupational tin miners in Yunnan, China. Sputum samples were collected prospectively at baseline and 7 annual screenings since enrollment. The associations between sputum cytologic results from baseline screening, the first 4 consecutive rounds of sputum screening, and lung cancer risk were analyzed by time-varying covariate Cox regression model.Results:A moderate or worse cytologic result was associated with a significantly increased lung cancer risk. This relative hazard significantly decreased over time. Compared with negative screening results, the adjusted hazard ratios of baseline-moderate or worse atypia, at least one moderate or worse atypia in the first 4 consecutive screening rounds during the first 10 years of follow-up were 3.11 [95% confidence interval (CI): 2.37–4.07], 3.25 (95% CI: 2.33–4.54) respectively. This association was stronger for persistent atypia (adjusted hazard ratio = 17.55, 95% CI: 8.32–37.03); atypia identified in the recent screening rounds (adjusted HR = 4.14, 95% CI: 2.70–6.35), and those were old in age, had higher level of smoking, occupational radon, and arsenic exposure. In terms of histology, this increased risk was significant for squamous cell carcinoma and small cell lung cancer.Conclusions:Although decreasing over time, an increased lung cancer risk concerning moderate or worse sputum atypia can continue at least for 10 years.Impact:Sputum atypia might be helpful for identifying high-risk individuals for screening, surveillance, or chemoprevention of lung cancer.
Applying the Strategic Planning Process to a Large Research Consortium: The Example of the National Cancer Institute Cohort Consortium
Authors: Harvey Chinonye E. , Gapstur Susan M. , Pottinger Camille A. , Elena Joanne W. , Helzlsouer Kathy J. 
Published: August 2021

Abstract
Strategic planning is conducted by many organizations to systematically evaluate and assess their current state, establish or update their mission and/or goals, and identify strategies and activities to achieve the goals. The National Cancer Institute (NCI) Cohort Consortium is a collaborative network of 62 prospective cohort studies and their affiliated investigators that focus on cancer etiology and outcome research. The organization's membership grew markedly from 10 cohort studies at its inception in 2001 to 59 cohort studies at the time of the launch of the Consortium's strategic planning in 2017. This paper describes the strategic planning process that was conducted to establish organizational goals and to develop strategies and activities consistent with the Consortium's mission. The process involved a 2-year iterative approach combining surveys and in-person meetings. The resulting goals focus on communication, career development, research facilitation, scientific gaps, and common scientific challenges. The NCI Cohort Consortium's strategic plan and evaluation of its progress will advance new initiatives in cancer etiology and survivorship research.
Obesity, Height, and Serum Androgen Metabolism among Postmenopausal Women in the Women's Health Initiative Observational Study
Authors: Oh Hannah , Wild Robert A. , Manson JoAnn E. , Bea Jennifer W. , Shadyab Aladdin H. , Pfeiffer Ruth M. , Saquib Nazmus , Underland Lisa , Anderson Garnet L. , Xu Xia , Trabert Britton 
Published: August 2021

Abstract

Background:
Anthropometric measures, including obesity, are important risk factors for breast and endometrial cancers in postmenopausal women. It is unknown whether these risk factors are associated with androgen metabolism, another risk factor for these cancers.

Methods:
Using baseline data from 1,765 postmenopausal women in the Women's Health Initiative Observational Study, we conducted a cross-sectional analysis examining associations between anthropometric measures [current body mass index (BMI), waist-to-hip ratio (WHR), height, and recalled BMI at age 18) and serum androgen metabolites. Twelve androgens/androgen metabolites were quantified using LC-MS/MS. Geometric means of androgen/androgen metabolite concentrations were estimated using linear regression, adjusting for potential confounders and stratified by hormone therapy (HT) use.

Results:
Regardless of HT use, higher current BMI (≥30 vs. &lt;25 kg/m2) was associated with higher serum concentrations of dehydroepiandrosterone sulfate (DHEAS), 5α-reduced glucuronide metabolites [androsterone-glucuronide (ADT-G), 5α-androstane-3α,17β diol-3-glucuronide (3α-diol-3G), 3α-diol-17-glucuronide (3α-diol-17G)], and DHEAS:DHEA ratio (all P trend ≤ 0.02). BMI was also positively associated with unconjugated estrone:androstenedione and unconjugated estradiol:testosterone ratios among never/former HT users (all P trend &lt; 0.001) but not among current users (P-int &lt; 0.001). WHR was positively associated with adrenal androgens and 5α-reduced glucuronide metabolites in obese women only (BMI ≥ 30 kg/m2; all P-trend ≤ 0.01). BMI at age 18 was inversely associated with adrenal androgens (DHEA, DHEAS, androstenedione, testosterone) and 5α-reduced glucuronide metabolites in never/former HT users (all P trend &lt; 0.06). Height was not associated with androgen metabolites.

Conclusions:
Current BMI is associated with androgen metabolism among postmenopausal women.

Impact:
This study contributes to our understanding of the link between obesity and cancer risk in postmenopausal women.
Recombinant protein production provoked accumulation of ATP, fructose-1,6-bisphosphate and pyruvate in E. coli K12 strain TG1
Authors: Weber Jan , Li Zhaopeng , Rinas Ursula 
Published: August 2021

Abstract
Background
Recently it was shown that production of recombinant proteins in E. coli BL21(DE3) using pET based expression vectors leads to metabolic stress comparable to a carbon overfeeding response. Opposite to original expectations generation of energy as well as catabolic provision of precursor metabolites were excluded as limiting factors for growth and protein production. On the contrary, accumulation of ATP and precursor metabolites revealed their ample formation but insufficient withdrawal as a result of protein production mediated constraints in anabolic pathways. Thus, not limitation but excess of energy and precursor metabolites were identified as being connected to the protein production associated metabolic burden.

Results
Here we show that the protein production associated accumulation of energy and catabolic precursor metabolites is not unique to E. coli BL21(DE3) but also occurs in E. coli K12. Most notably, it was demonstrated that the IPTG-induced production of hFGF-2 using a tac-promoter based expression vector in the E. coli K12 strain TG1 was leading to persistent accumulation of key regulatory molecules such as ATP, fructose-1,6-bisphosphate and pyruvate.

Conclusions
Excessive energy generation, respectively, accumulation of ATP during recombinant protein production is not unique to the BL21(DE3)/T7 promoter based expression system but also observed in the E. coli K12 strain TG1 using another promoter/vector combination. These findings confirm that energy is not a limiting factor for recombinant protein production. Moreover, the data also show that an accelerated glycolytic pathway flux aggravates the protein production associated “metabolic burden”. Under conditions of compromised anabolic capacities cells are not able to reorganize their metabolic enzyme repertoire as required for reduced carbon processing.
The current issues and future perspective of artificial intelligence for developing new treatment strategy in non-small cell lung cancer: harmonization of molecular cancer biology and artificial intelligence
Authors: Tanaka Ichidai , Furukawa Taiki , Morise Masahiro 
Published: August 2021

AbstractComprehensive analysis of omics data, such as genome, transcriptome, proteome, metabolome, and interactome, is a crucial technique for elucidating the complex mechanism of cancer onset and progression. Recently, a variety of new findings have been reported based on multi-omics analysis in combination with various clinical information. However, integrated analysis of multi-omics data is extremely labor intensive, making the development of new analysis technology indispensable. Artificial intelligence (AI), which has been under development in recent years, is quickly becoming an effective approach to reduce the labor involved in analyzing large amounts of complex data and to obtain valuable information that is often overlooked in manual analysis and experiments. The use of AI, such as machine learning approaches and deep learning systems, allows for the efficient analysis of massive omics data combined with accurate clinical information and can lead to comprehensive predictive models that will be desirable for further developing individual treatment strategies of immunotherapy and molecular target therapy. Here, we aim to review the potential of AI in the integrated analysis of omics data and clinical information with a special focus on recent advances in the discovery of new biomarkers and the future direction of personalized medicine in non-small lung cancer.
Family doctor contract services and health-related quality of life among patients with chronic diseases in rural China: what is the role of socioeconomic status?
Authors: Li Zhixian , Li Jie , Fu Peipei , Chen Yan , Jing Zhengyue , Yuan Yemin , Yang Shijun , Yan Chen , Li Wenjuan , Li Jie , Gui Zhen , Zhou Chengchao 
Published: August 2021

Abstract
Purpose
Few studies explored the relationship between the family doctor contract services (FDCS) and health-related quality of life (HRQOL) among patients with chronic diseases in rural China. This study aims to explore the relationship between the status of signing on FDCS and HRQOL among patients with chronic diseases and examine whether there are differences in the relationship between different socioeconomic status (SES).

Methods
A total of 1,210 respondents were included in this study. HRQOL was measured by EQ-5D-3L. The contracting status was divided into uncontracted and contracted. Tobit regression and Logistic regression were employed to explore the association between contracting status and HRQOL. The interaction terms were included to explore the differences in the association among different SES.

Results
Contracting with family doctors was associated with HRQOL (coefficient = 0.042; 95%CI 0.008 to 0.075). The association was different among different socioeconomic levels that the contracting status was only associated with HRQOL in sub-high-income (P < 0.01) and highly educated patients (P < 0.05). Compared with uncontracted patients, contracted patients reported higher ED-5D-3L utility value in the sub-high-income group (coefficient = 0.078; 95%CI 0.017 to 0.140) and high educational attainment (coefficient = 0.266; 95%CI 0.119 to 0.413).

Conclusions
This study found a significant association between FDCS and HRQOL among chronic patients in rural Shandong, China. This relationship varied by income levels and educational attainment. The government should take efforts to formulate a variety of measures to encourage chronic patients to contract with family doctors, with special attention to people with low SES.
Sirtuin3 rs28365927 functional variant confers to the high risk of non-alcoholic fatty liver disease in Chinese Han population
Authors: Chen Li-jie , Guo Jing , Zhang Song-xia , Xu Ying , Zhao Qing , Zhang Wei , Xiao Jian , Chen Yao 
Published: August 2021

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition associated with aging, insulin resistance, metabolic syndrome, genetic factors and more. Although genetic traits are among the most important risks factors for NAFLD, the understanding of their influence is still quite limited. The present study aimed at identifying novel single nucleotide polymorphisms (SNPs) that may confer a risk for NAFLD in the Han Chinese population.

Methods
Based on the “two-hit hypothesis”, candidate SNPs, including Sirtuin3 rs28365927, were genotyped by MassARRAY in B-type ultrasonography-proven NAFLD patients (n = 292) and healthy controls (n = 387).

Results
In a model analysis of individuals matched based on gender and age that compared 223 NAFLD and 223 non-NAFLD patients, the rs28365927 GA + AA genotype was a significant risk factor for the development of NAFLD in a dominant model. Rs28365927 was significantly associated with a higher NAFLD risk in both an additive model (A vs G) and genotypic model (GA vs GG). Among the NAFLD patients, serum levels of total bilirubin (TBIL), DBIL direct bilirubin (DBIL) and glutamic-pyruvic transaminase (ALT) in rs28365927 A allele carriers (GA + AA) were 11.1, 14.7 and 41.5% higher, respectively, than in non-carriers (GG). Furthermore, among the NAFLD patients, the carriers of Rs28365927 allele A were positively correlated with higher ALT levels.

Conclusion
Sirtuin3 rs28365927 functional variant confers to the high risk of non-alcoholic fatty liver disease in Chinese Han population. The rs28365927 A allele significantly increased the ALT levels of NAFLD patients.
Biological consequences of cancer radiotherapy in the context of oral squamous cell carcinoma
Authors: Feller G. , Khammissa R. A. G. , Nemutandani M. S. , Feller L. 
Published: August 2021

AbstractApproximately 50% of subjects with cancer have been treated with ionizing radiation (IR) either as a curative, adjuvant, neoadjuvant or as a palliative agent, at some point during the clinical course of their disease. IR kills cancer cells directly by injuring their DNA, and indirectly by inducing immunogenic cell killing mediated by cytotoxic T cells; but it can also induce harmful biological responses to non-irradiated neighbouring cells (bystander effect) and to more distant cells (abscopal effect) outside the primary tumour field of irradiation.Although IR can upregulate anti-tumour immune reactions, it can also promote an immunosuppressive tumour microenvironment. Consequently, radiotherapy by itself is seldom sufficient to generate an effective long lasting immune response that is capable to control growth of metastasis, recurrence of primary tumours and development of second primary cancers. Therefore, combining radiotherapy with the use of immunoadjuvants such as immune checkpoint inhibitors, can potentiate IR-mediated anti-tumour immune reactions, bringing about a synergic immunogenic cell killing effect.The purpose of this narrative review is to discuss some aspects of IR-induced biological responses, including factors that contributes to tumour radiosensitivity/radioresistance, immunogenic cell killing, and the abscopal effect.
The effects of maternal alcohol consumption during pregnancy on adverse fetal outcomes among pregnant women attending antenatal care at public health facilities in Gondar town, Northwest Ethiopia: a prospective cohort study
Authors: Addila Alemu Earsido , Azale Telake , Gete Yigzaw Kebede , Yitayal Mezgebu 
Published: August 2021

Abstract
Background
The teratogenic effect of fetal alcohol exposure may lead to actual and potential problems, instantly after birth, at infancy; or even later, and mental impairment in life. This study aimed to investigate the effects of maternal alcohol consumption during pregnancy on adverse fetal outcomes at Gondar town public health facilities, Northwest Ethiopia.

Methods
A facility-based prospective cohort study was performed among 1778 pregnant women who were booked for antenatal care in selected public health facilities from 29 October 2019 to 7 May 2020 in Gondar town. We used a two-stage random sampling technique to recruit and include participants in the cohort. Data were collected using the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C) standardized and pre-tested questionnaire. Multivariable analysis was performed to examine the association between reported prenatal alcohol exposure (non-hazardous and hazardous) and interested adverse birth outcomes using log-binomial regression modeling. The burden of outcomes was reported using the adjusted risk ratio and population-attributable risk (PAR).

Results
A total of 1686 pregnant women were included in the analysis, which revealed that the incidences of low birth weight, preterm, and stillbirth were 12.63% (95% CI: 11.12, 14.31), 6.05% (95% CI: 5.00, 7.29) and 4.27% (95% CI: 3.4, 5.35), respectively. Non-hazardous and hazardous alcohol consumption during pregnancy was significantly associated with low birth weight (ARR = 1.50; 95% CI: 1.31, 1.98) and (ARR = 2.34; 95% CI: 1.66, 3.30), respectively. Hazardous alcohol consumption during pregnancy was also significantly associated with preterm birth (ARR = 2.06; 95% CI: 1.21, 3.52). The adjusted PAR of low birth weight related to non-hazardous and hazardous alcohol drinking during pregnancy was 11.72 and 8.44%, respectively. The adjusted PAR of hazardous alcohol consumption was 6.80% for preterm.

Conclusions
Our findings suggest that there is an increasing risk of adverse birth outcomes, particularly preterm delivery and low birth weight, with increasing levels of alcohol intake. This result showed that the prevention of maternal alcohol use during pregnancy has the potential to reduce low birth weight and preterm birth. Hence, screening women for alcohol use during antenatal care visits and providing advice with rigorous follow-up of women who used alcohol may save the fetus from the potential risks of adverse birth outcomes.
Video assisted, transaortic removal of left ventricular thrombus during concurrent cardiac surgery: a case report
Authors: Eranki Aditya , Villanueva Claudia , Collins Nicholas , Seah Peng 
Published: August 2021

Abstract
Introduction
Left ventricular (LV) thrombus is a complication of acute myocardial infarction and is associated with systemic thromboembolism. We describe a trans-aortic endoscopic approach to the removal of an LV thrombus in a patient undergoing concurrent coronary artery bypass grafting and aortic valve replacement.

Case presentation
A 47 year old male presented following an embolic middle cerebral artery stroke and underwent transthoracic echocardiography demonstrating a mobile LV thrombus. Additional investigation revealed a moderately stenosed bicispid aortic valve, two vessel coronary artery disease and ischemic cardiomyopathy. The patient underwent early surgery to reduce the risk of further embolic episodes. A trans-aortic approach was utilized with videoscopy and single shafted instrumentation to aide in removal of the thrombus. The patient then underwent aortic valve replacement and coronary artery bypass grafting.

Conclusion
We report an alternative technique for the removal of a left ventricular thrombus in a patient undergoing concurrent coronary and aortic valve surgery. The transaortic video-assisted approach provided excellent visualisation of the apex and near complete removal of the thrombus without damaging the surrounding trabeculae. The main benefit of this technique is sparing of LV tissue, thereby preserving left ventricular function.