bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining protein and metabolic engineering strategies for biosynthesis of melatonin in Escherichia coli
Authors: Zhang Yanfeng , He Yongzhi , Zhang Nan , Gan JiaJia , Zhang Shan , Dong Zhiyang 
Published: August 2021

Abstract
Background
Melatonin has attracted substantial attention because of its excellent prospects for both medical applications and crop improvement. The microbial production of melatonin is a safer and more promising alternative to chemical synthesis approaches. Researchers have failed to produce high yields of melatonin in common heterologous hosts due to either the insolubility or low enzyme activity of proteins encoded by gene clusters related to melatonin biosynthesis.

Results
Here, a combinatorial gene pathway for melatonin production was successfully established in Escherichia coli by combining the physostigmine biosynthetic genes from Streptomyces albulus and gene encoding phenylalanine 4-hydroxylase (P4H) from Xanthomonas campestris and caffeic acid 3-O-methyltransferase (COMT) from Oryza sativa. A threefold improvement of melatonin production was achieved by balancing the expression of heterologous proteins and adding 3% glycerol. Further protein engineering and metabolic engineering were conducted to improve the conversion of N-acetylserotonin (NAS) to melatonin. Construction of COMT variant containing C303F and V321T mutations increased the production of melatonin by fivefold. Moreover, the deletion of speD gene increased the supply of S-adenosylmethionine (SAM), an indispensable cofactor of COMT, which doubled the yield of melatonin. In the final engineered strain EcMEL8, the production of NAS and melatonin reached 879.38 ± 71.42 mg/L and 136.17 ± 1.33 mg/L in a shake flask. Finally, in a 2-L bioreactor, EcMEL8 produced 1.06 ± 0.07 g/L NAS and 0.65 ± 0.11 g/L melatonin with tryptophan supplementation.

Conclusions
This study established a novel combinatorial pathway for melatonin biosynthesis in E. coli and provided alternative strategies for improvement of melatonin production.
Knockdown lncRNA CRNDE enhances temozolomide chemosensitivity by regulating autophagy in glioblastoma
Authors: Zhao Zijin , Liu Miaomiao , Long Wenyong , Yuan Jian , Li Haoyu , Zhang Chi , Tang Guodong , Jiang Weixi , Yuan Xianrui , Wu Minghua , Liu Qing 
Published: August 2021

Abstract
Background
The regulatory roles of long non-coding RNA (lncRNA) CRNDE in temozolomide (TMZ) chemoresistance to glioblastoma multiforme (GBM) are still poorly understood. Therefore, the function, characteristics, and possible mechanism of CRNDE in TMZ-induced chemoresistance to GBM were explored.

Methods
Firstly, the expression level of CRNDE in 58 cases of glioma tissue specimens and 30 cases of normal brain tissues were tested by qRT-PCR. Meanwhile, the correlation between CRNDE expression level, the clinicopathological characteristics, and survival time of patients with glioma were analyzed. Then, the CRNDE expression in various glioma cell lines was detected, and CRNDE knockdown cell models were constructed. Subsequently, to explore the effect of CRNDE on chemosensitivity to TMZ, cell viability was detected by the CCK-8 assay and IC50 values, and cell proliferation was detected by cell clone assay and EdU assay, as well as cell survival was detected by apoptosis with flow cytometry under TMZ treatment. Further, the expression of drug-resistance protein ABCG2, autophagy related proteins, and PI3K/Akt/mTOR pathway were measured by western blot or qRT-PCR in TMZ-treated glioma cells. Finally, the mouse tumor xenograft model was established and the tumor volume and weight were measured, and ABCG2 expression was conducted by immunohistochemistry assay.

Results
The integrated results demonstrated lncRNA CRNDE was a poor prognosis factor for GBM patient, which was upregulated in patients who were resistant to TMZ, and closely associated with chemotherapeutic response status to TMZ treatment. Further, functional assays revealed that knockdown of CRNDE could notably reduce glioma cell viability and proliferation, and elevate cell apoptosis to enhance the chemosensitivity to TMZ in vitro and in vivo. Mechanistically, the depression of CRNDE could diminish the expression of LC3 II/I, Beclin1 and Atg5 and increase the p62 expression level to inhibit autophagy due to the activation of PI3K/Akt/mTOR pathway as well as highly correlated with ABCG2 expression.

Conclusions
Overall, the study provided that lncRNA CRNDE is a reliable clinical predictor of outcome and prognosis and a potential biomarker for predicting TMZ treatment response in GBM by modulating the autophagy through PI3K/Akt/mTOR pathway and ABCG2 expression which may be a novel therapeutic target for regulating TMZ sensitivity to GBM.
The role of the deubiquitinating enzyme DUB3/USP17 in cancer: a narrative review
Authors: Yang Guang-Fei , Zhang Xin , Su Yi-Ge , Zhao Ren , Wang Yan-Yang 
Published: August 2021

AbstractThe balance between ubiquitination and deubiquitination is critical for the degradation, transport, localization, and activity of proteins. Deubiquitinating enzymes (DUBs) greatly contribute to the balance of ubiquitination and deubiquitination, and they have been widely studied due to their fundamental role in cancer. DUB3/ubiquitin-specific protease 17 (USP17) is a type of DUB that has attracted much attention in cancer research. In this review, we summarize the biological functions and regulatory mechanisms of USP17 in central nervous system, head and neck, thoracic, breast, gastrointestinal, genitourinary, and gynecologic cancers as well as bone and soft tissue sarcomas, and we provide new insights into how USP17 can be used in the management of cancer.
Lymphocyte activating gene 3 protein expression in nasopharyngeal carcinoma is correlated with programmed cell death-1 and programmed cell death ligand-1, tumor-infiltrating lymphocytes
Authors: Luo Fan , Cao Jiaxin , Lu Feiteng , Zeng Kangmei , Ma Wenjuan , Huang Yan , Zhang Li , Zhao Hongyun 
Published: August 2021

AbstractBackgroundImmunotherapy has shown promising efficacy in patients with nasopharyngeal carcinoma (NPC). Lymphocyte activating 3 gene (LAG-3) represents a significant immune target, however, its relationship with NPC remains unclear. This study aimed to evaluate LAG-3 expression in NPC and its association with CD3+ tumor-infiltrating lymphocytes (TILs), Granzyme B (GZMB), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) expression.MethodsA total of 182 patients with NPC from Sun Yat-sen University Cancer Center, China, were included in this retrospective study. LAG-3 expression in 15 NPC cell lines and LAG-3, CD3+ TILs, GZMB, PD-L1 and PD-1 in clinical samples were estimated using immunohistochemistry. The Chi-square test was used to estimate the association between LAG-3, other biomarkers, and clinical characteristics. Survival analysis was performed using the Kaplan–Meier method and the Cox regression model.ResultsLAG-3 was negatively expressed in all of the 15 NPC cell lines, whereas, 147 patients with NPC (80.8%) exhibited high LAG-3 expression on TILs from tumor tissues. Male patients and those who were EBV-positive presented higher LAG-3 expression. Correlation analyses showed that LAG-3 expression was related to PD-1 expression on TILs, as well as, PD-L1 expression on tumor cells (TCs) and TILs. Both the univariate and multivariate Cox models indicated that pathological type III (P = 0.036), higher LAG-3 on TILs (P < 0.001), higher PD-L1 on TCs (P = 0.027), and higher PD-1 on TILs (P < 0.001) were associated with poorer disease-free survival (DFS). However, lower PD-L1 expression on TILs was related to superior DFS only in the univariate Cox analyses (P = 0.002).ConclusionHigher LAG-3 and PD-1 on TILs, and higher PD-L1 expression on TCs, and pathological type III were identified as independent risk factors for poorer DFS in NPC patients. Our data demonstrate that LAG-3 is a promising inhibitory receptor that may play an important role in anti-NPC therapy.
Assessing community knowledge, attitude and practices to strengthen communication strategy for Malaria Elimination Demonstration Project in Mandla
Authors: Rajvanshi Harsh , Saha Kalyan B. , Sharma Ravendra K. , Bharti Praveen K. , Nisar Sekh , Jayswar Himanshu , Mishra Ashok K. , Shukla Man Mohan , Das Aparup , Kaur Harpreet , Wattal Suman L. , Lal Altaf A. 
Published: August 2021

Abstract
Background
Changes in social, belief, and behavioural practices are essential for the success of any public health delivery programme. In the planning stages of the Malaria Elimination Demonstration Project (MEDP), priority was given to communication with a goal to develop capacity of health workers and to improve the knowledge, attitude and practices (KAP) of the people of Mandla. This paper describes the level of community knowledge on malaria, including its prevention, diagnosis, treatment-seeking behaviour, and the level of satisfaction with the services provided by the project.

Methods
A cross sectional survey was undertaken in 1233 villages of Mandla to study the KAP and self-assessed improvement in knowledge and satisfaction level of the community. The goal of the study was to understand whether there is need for strengthening communication strategy of MEDP for better impact. The survey was conducted amongst the head/eligible members of the 733 households located in the nine blocks of the district using clustered random sampling.

Results
Though four-fifths of the respondents were able to correlate the transmission of malaria with mosquitoes, misconceptions existed among them. The types of malaria were not known to everyone. Only 39% were aware of the Indoor Residual Spray (IRS) and 41% understood the value of Long-Lasting Insecticidal Nets (LLIN). Around 71% of subjects surveyed were aware of the proper diagnostic tests for malaria. A total of 87% of the respondents knew about the MEDP staff working in their respective villages.

Conclusion
The study reported gaps in knowledge on malaria at community level. The self-assessment of the community revealed that the communication strategy established by MEDP in Mandla district has been useful to them as they are becoming better informed about the prevention and treatment aspects of disease. The lessons learned as revealed in the KAP survey will improve malaria elimination outcomes in a timely manner.
Comparing insecticide-treated nets access-use based on universal household and population indicators vis-a-vis measures adapted to sleeping spaces in Ethiopia
Authors: Kebede Yohannes , Sudhakar Morankar , Alemayehu Guda , Abebe Lakew , Birhanu Zewdie 
Published: August 2021

Abstract
Background
Insecticide-treated nets (ITNs) access-use has been pivotal monitoring indicator for malaria prevention and control, particularly in resource limited settings. The objective of the study was to compare ITN access-use based on universal household and population indicators and measures adapted to sleeping spaces.

Methods
A cross-sectional study was conducted in five districts of Jimma Zone, Ethiopia, March, 2019. 762 HHs were sampled for the survey. Multi-stage followed by simple random sampling used. Monitoring and evaluation reference group’s (MERG’s) indicators were used for measuring ITN access-use. MERG’s indicators are each adapted ITN access-use to sleeping spaces. Household (ownership, saturation and sufficiency) and population access and household members’ status of last night sleeping under ITN compared based on the two models. Differences of estimates of ITN access-use based on the two methods reported as magnitude of over/under estimations, at p-value < 0.05.

Results
Based on MERG’s approach, the study revealed household (HH) based indicators as such: HH ownership of at least 1 ITN (92.6%), sufficiency of ITN for every two people in HH (50.3%), and saturation of ITN for every 2 people in HHs with any ITN (54.6%). Moreover, population based indicators were: population with ITN access (P3 = 78.6%), people who slept under ITN previous night (63.0%), people who slept under ITN among who accessed it (73.1%), ITN use-gap (26.9%). Equivalent indicators of HH ownership, sufficiency, saturation, and people accessed at where they actually slept, and people slept under ITN among those accessed at where they slept estimated at 71.3%, 49.4%, 69.3%, 66.3%, and 92.1%, respectively. MERG’s approach over-estimated ownership, people’s access, and behaviour-failures by 21.3%, 12.3%, 19.0%, respectively. Over-estimation occurred for reasons such as many sleeping spaces lack ITN and > 2 people actually slept per sleeping space.

Conclusions
MERG’s universal indicators over estimated households and populations ITN access-use as a result of absence of measures capturing access-use values at spaces where people actually slept. Consequently, measures adapted to sleeping contexts revealed potential misdistributions practiced when the existing indicators are in use. Insertion of sleeping spaces into existing approach will be worthwhile and needs to be promoted as it improves curiosity in ITN distribution, produces closer estimates and prevents malaria prevention and control programmes from overlooking access-use challenges.
High-resolution probe design for measuring the dielectric properties of human tissues
Authors: Wang Xinran , Guo Hongfu , Zhou Chen , Bai Junkai 
Published: August 2021

Abstract
Background
In order to use the microwave to measure the dielectric constant of the human body and improve the measurement resolution, a small near-field probe working at 915 MHz is designed in this paper.

Method
Based on the electric small loop antenna model loaded by the spiral resonator (SR), a small near-field probe was designed. The probe model is designed and optimized by the HFSS (high frequency structure simulator) software. The human tissues were tested by the manufactured probe and the relationship between the S11 parameters of the probe and the human tissues was analyzed.

Results and conclusions
A probe with small size was designed and fabricated, with the overall size of 10.0 mm × 12.0 mm × 0.8 mm. The probe has a good performance with a 30.7 dB return loss, a 20 MHz bandwidth at the resonance point, and a distance resolution of 10 mm. Due to the small size and good resolution of the probe, it can be used in the measurement of human tissues.
The pathways from perceived discrimination to self-rated health among the Chinese diaspora during the COVID-19 pandemic: investigation of the roles of depression, anxiety, and social support
Authors: Chen Youli , Wang Zicong , Dong Weizhen , Xu Jia Huei Chen , Wu Sizhe Ji , Zhang Xiangyang , Chen Chun 
Published: August 2021

Abstract
Background
Research indicates the adverse impacts of perceived discrimination on health, and discrimination inflamed by the COVID-19 pandemic, a type of social exclusion, could affect the well-being of the Chinese diaspora. We analyzed the relationship and pathways of perceived discrimination’s effect on health among the Chinese diaspora in the context of the pandemic to contribute to the literature on discrimination in this population under the global public health crisis.

Methods
We analyzed data from 705 individuals of Chinese descent residing in countries outside of China who participated in a cross-sectional online survey between April 22 and May 9, 2020. This study utilized a structural equation model (SEM) to evaluate both direct and indirect effects of perceived discrimination on self-rated health (SRH) and to assess the mediating roles of psychological distress (namely, anxiety and depression) and social support from family and friends.

Results
This online sample comprised predominantly young adults and those of relatively high socioeconomic status. This study confirmed the total and direct effect of recently perceived discrimination on SRH and found the indirect effect was mainly mediated by depression. Mediating roles of anxiety and social support on the discrimination-health relationship were found insignificant in this SEM.

Conclusions
Our findings suggest discrimination negatively affected the well-being of the Chinese diaspora, and depression acted as a major mediator between the discrimination-health relationship. Therefore, interventions for reducing discrimination to preserve the well-being of the Chinese diaspora are necessary. Prompt intervention to address depression may partially relieve the disease burden caused by the surge of discrimination.
Associations between polyfluoroalkyl substance and organophosphate flame retardant exposures and telomere length in a cohort of women firefighters and office workers in San Francisco
Authors: Clarity Cassidy , Trowbridge Jessica , Gerona Roy , Ona Katherine , McMaster Michael , Bessonneau Vincent , Rudel Ruthann , Buren Heather , Morello-Frosch Rachel 
Published: August 2021

AbstractBackgroundEnvironmental chemical exposures can affect telomere length, which in turn has been associated with adverse health outcomes including cancer. Firefighters are occupationally exposed to many hazardous chemicals and have higher rates of certain cancers. As a potential biomarker of effect, we assessed associations between chemical exposures and telomere length in women firefighters and office workers from San Francisco, CA.MethodsWe measured serum concentrations of polyfluoroalkyl substances (PFAS), urinary metabolites of flame retardants, including organophosphate flame retardants (OPFRs), and telomere length in peripheral blood leukocytes in women firefighters (N = 84) and office workers (N = 79) who participated in the 2014–15 Women Workers Biomonitoring Collaborative. Multiple linear regression models were used to assess associations between chemical exposures and telomere length.ResultsRegression results revealed significant positive associations between perfluorooctanoic acid (PFOA) and telomere length and perfluorooctanesulfonic acid (PFOS) and telomere length among the whole cohort. Models stratified by occupation showed stronger and more significant associations among firefighters as compared to office workers. Among firefighters in models adjusted for age, we found positive associations between telomere length and log-transformed PFOA (β(95%CI) = 0.57(0.12, 1.02)), PFOS (0.44 (0.05, 0.83)), and perfluorodecanoic acid (PFDA) (0.43 (0.02, 0.84)). Modeling PFAS as categories of exposure showed significant associations between perfluorononanoic acid (PFNA) and telomere length among firefighters. Significant associations between OPFR metabolites and telomere length were seen for bis (1,3-dichloro-2-propyl) phosphate (BDCPP) and telomere length among office workers (0.21(0.03, 0.40)) and bis (2-chloroethyl) phosphate (BCEP) and telomere length among firefighters (− 0.14(− 0.28, − 0.01)). For OPFRs, the difference in the direction of effect by occupational group may be due to the disparate detection frequencies and concentrations of exposure between the two groups and/or potential unmeasured confounding.ConclusionOur findings suggest positive associations between PFAS and telomere length in women workers, with larger effects seen among firefighters as compared to office workers. The OPFR metabolites BDCPP and BCEP are also associated with telomere length in firefighters and office workers. Associations between chemical exposures and telomere length reported here and by others suggest mechanisms by which these chemicals may affect carcinogenesis and other adverse health outcomes.
Development of a Web GIS for small-scale detection and analysis of COVID-19 (SARS-CoV-2) cases based on volunteered geographic information for the city of Cologne, Germany, in July/August 2020
Authors: Schmidt Fabian , Dröge-Rothaar Arne , Rienow Andreas 
Published: August 2021

Abstract
Background
Various applications have been developed worldwide to contain and to combat the coronavirus disease-19 (COVID-19) pandemic. In this context, spatial information is always of great significance. The aim of this study is to describe the development of a Web GIS based on open source products for the collection and analysis of COVID-19 cases and its feasibility in terms of technical implementation and data protection.

Methods
With the help of this Web GIS, data on this issue were collected voluntarily from the Cologne area. Using house perimeters as a data basis, it was possible to check, in conjunction with the Official Topographic Cartographic Information System object type catalog, whether buildings with certain functions, for example residential building with trade and services, have been visited more frequently by infected persons than other types of buildings. In this context, data protection and ethical and legal issues were considered.

Results
The results of this study show that the development of a Web GIS for the generation and evaluation of volunteered geographic information (VGI) with the help of open source software is possible. Furthermore, there are numerous data protection and ethical and legal aspects to consider, which not only affect VGI per se but also affect IT security.

Conclusions
From a data protection perspective, more attention needs to be paid to the intervention and post-processing of data. In addition, official data must always be used as a reference for the actual spatial consideration of the number of infections. However, VGI provides added value at a small-scale level, so that valid information can also be reliably derived in the context of health issues. The creation of guidelines for the consideration of data protection, ethical aspects, and legal requirements in the context of VGI-based applications must also be considered.
Trial registration The article does not report the results of a health care intervention for human participants
Uncovering cancer vulnerabilities by machine learning prediction of synthetic lethality
Authors: Benfatto Salvatore , Serçin Özdemirhan , Dejure Francesca R. , Abdollahi Amir , Zenke Frank T. , Mardin Balca R. 
Published: August 2021

AbstractBackgroundSynthetic lethality describes a genetic interaction between two perturbations, leading to cell death, whereas neither event alone has a significant effect on cell viability. This concept can be exploited to specifically target tumor cells. CRISPR viability screens have been widely employed to identify cancer vulnerabilities. However, an approach to systematically infer genetic interactions from viability screens is missing.MethodsHere we describe PAn-canceR Inferred Synthetic lethalities (PARIS), a machine learning approach to identify cancer vulnerabilities. PARIS predicts synthetic lethal (SL) interactions by combining CRISPR viability screens with genomics and transcriptomics data across hundreds of cancer cell lines profiled within the Cancer Dependency Map.ResultsUsing PARIS, we predicted 15 high confidence SL interactions within 549 DNA damage repair (DDR) genes. We show experimental validation of an SL interaction between the tumor suppressor CDKN2A, thymidine phosphorylase (TYMP) and the thymidylate synthase (TYMS), which may allow stratifying patients for treatment with TYMS inhibitors. Using genome-wide mapping of SL interactions for DDR genes, we unraveled a dependency between the aldehyde dehydrogenase ALDH2 and the BRCA-interacting protein BRIP1. Our results suggest BRIP1 as a potential therapeutic target in ~ 30% of all tumors, which express low levels of ALDH2.ConclusionsPARIS is an unbiased, scalable and easy to adapt platform to identify SL interactions that should aid in improving cancer therapy with increased availability of cancer genomics data.