bluuebunny/crossref_metadata_2025_split huggingface dataset:
LED control of gene expression in a nanobiosystem composed of metallic nanoparticles and a genetically modified E. coli strain
Authors: Aratboni Hossein Alishah , Rafiei Nahid , Khorashad Larousse Khosravi , Lerma-Escalera Albert Isaac , Balderas-Cisneros Francisco de Jesús , Liu Zhaowei , Alemzadeh Abbas , Shaji Sadasivan , Morones-Ramírez José Ruben 
Published: June 2021

Abstract
Background
Within the last decade, genetic engineering and synthetic biology have revolutionized society´s ability to mass-produce complex biological products within genetically-modified microorganisms containing elegantly designed genetic circuitry. However, many challenges still exist in developing bioproduction processes involving genetically modified microorganisms with complex or multiple gene circuits. These challenges include the development of external gene expression regulation methods with the following characteristics: spatial–temporal control and scalability, while inducing minimal permanent or irreversible system-wide conditions. Different stimuli have been used to control gene expression and mitigate these challenges, and they can be characterized by the effect they produce in the culture media conditions. Invasive stimuli that cause permanent, irreversible changes (pH and chemical inducers), non-invasive stimuli that cause partially reversible changes (temperature), and non-invasive stimuli that cause reversible changes in the media conditions (ultrasound, magnetic fields, and light).

Methods
Opto-control of gene expression is a non-invasive external trigger that complies with most of the desired characteristics of an external control system. However, the disadvantage relies on the design of the biological photoreceptors and the necessity to design them to respond to a different wavelength for every bioprocess needed to be controlled or regulated in the microorganism. Therefore, this work proposes using biocompatible metallic nanoparticles as external controllers of gene expression, based on their ability to convert light into heat and the capacity of nanotechnology to easily design a wide array of nanostructures capable of absorbing light at different wavelengths and inducing plasmonic photothermal heating.

Results
Here, we designed a nanobiosystem that can be opto-thermally triggered using LED light. The nanobiosystem is composed of biocompatible gold nanoparticles and a genetically modified E. coli with a plasmid that allows mCherry fluorescent protein production at 37 °C in response to an RNA thermometer.

Conclusions
The LED-triggered photothermal protein production system here designed offers a new, cheaper, scalable switchable method, non-destructive for living organisms, and contribute toward the evolution of bioprocess production systems.
Dipstick proteinuria and risk of type 2 diabetes mellitus: a nationwide population-based cohort study
Authors: Jeon Jimin , Kim Jinkwon 
Published: June 2021

AbstractBackgroundProteinuria has been recognized as a marker of systemic inflammation and endothelial dysfunction associated with insulin resistance and β-cell impairment, which can contribute to the development of type 2 diabetes mellitus (T2DM). However, it is unknown whether the dipstick proteinuria test has a predictive value for new-onset T2DM.MethodsThis retrospective cohort study analyzed 239,287 non-diabetic participants who participated in the Korean nationwide health screening program in 2009–2010. Proteinuria was determined by the urine dipstick test at the baseline health screening. We performed multivariate Cox proportional regression analyses for the development of new-onset T2DM. Follow-up was performed until December 2015.ResultsDuring the mean follow-up period of 5.73 years, 22,215 participants were diagnosed with new-onset T2DM. The presence of proteinuria was significantly associated with an increased risk of T2DM (adjusted hazard ratio: 1.19, 95% confidence interval: 1.10, 1.29). There was a positive dose–response relationship between the degree of dipstick proteinuria and T2DM risk. This significant association between proteinuria and T2DM risk was consistent regardless of the fasting glucose level at baseline.ConclusionsDipstick proteinuria is a significant risk factor for new-onset T2DM. Therefore, proteinuria might be a useful biomarker to identify those at a high risk for developing T2DM.
Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients
Authors: Zhang Wei , Lin Liewen , Xia Ligang , Cai Wanxia , Dai Weier , Zou Chang , Yin Lianghong , Tang Donge , Xu Yong , Dai Yong 
Published: June 2021

Abstract
Background
The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. However, no prognostic biomarker has been applied for colorectal cancer (CRC) in the clinic.

Methods
Integrated with transcriptomic data from public databases, multi-omics examinations were conducted to search prognostic biomarkers for CRC. Moreover, the potential biological functions and regulatory mechanism of these predictive genes were also explored.

Results
In this study, we revealed that three mitochondrial genes were associated with the poor prognosis of CRC. Integrated analyses of transcriptome and proteome of CRC patients disclosed numerous down-regulated mitochondrial genes at both mRNA and protein levels, suggesting a vital role of mitochondria in carcinogenesis. Combined with the bioinformatics studies of transcriptomic datasets of 538 CRC patients, three mitochondrial prognostic genes were eventually selected out, including HIGD1A, SUCLG2, and SLC25A24. The expression of HIGD1A exhibited a significant reduction in two subtypes of adenoma and six subtypes of CRC, while the down-regulation of SUCLG2 and SLC25A24 showed more advantages in rectal mucinous adenocarcinoma. Moreover, we unveiled that these three genes had common expressions and might collaboratively participate in the synthesis of ribosomes. Our original multi-omics datasets, including DNA methylation, structural variants, chromatin accessibility, and phosphoproteome, further depicted the altered modifications on their potential transcriptional factors.

Conclusions
In summary, HIGD1A, SUCLG2, and SLC25A24 might serve as predictive biomarkers for CRC. The biological activities they involved in and their upstream regulators we uncovered would provide a functional context for the further-in-depth mechanism study.

Graphic abstract
Large-scale literature mining to assess the relation between anti-cancer drugs and cancer types
Authors: Bauer Chris , Herwig Ralf , Lienhard Matthias , Prasse Paul , Scheffer Tobias , Schuchhardt Johannes 
Published: June 2021

Abstract
Background
There is a huge body of scientific literature describing the relation between tumor types and anti-cancer drugs. The vast amount of scientific literature makes it impossible for researchers and physicians to extract all relevant information manually.

Methods
In order to cope with the large amount of literature we applied an automated text mining approach to assess the relations between 30 most frequent cancer types and 270 anti-cancer drugs. We applied two different approaches, a classical text mining based on named entity recognition and an AI-based approach employing word embeddings. The consistency of literature mining results was validated with 3 independent methods: first, using data from FDA approvals, second, using experimentally measured IC-50 cell line data and third, using clinical patient survival data.

Results
We demonstrated that the automated text mining was able to successfully assess the relation between cancer types and anti-cancer drugs. All validation methods showed a good correspondence between the results from literature mining and independent confirmatory approaches. The relation between most frequent cancer types and drugs employed for their treatment were visualized in a large heatmap. All results are accessible in an interactive web-based knowledge base using the following link: https://knowledgebase.microdiscovery.de/heatmap.

Conclusions
Our approach is able to assess the relations between compounds and cancer types in an automated manner. Both, cancer types and compounds could be grouped into different clusters. Researchers can use the interactive knowledge base to inspect the presented results and follow their own research questions, for example the identification of novel indication areas for known drugs.
Factors affecting the duration of coronary artery lesions in patients with the Kawasaki disease: a retrospective cohort study
Authors: Zhang Xuting , He Yuee , Shao Yiping , Hang Biyao , Xu Zhipeng , Chu Maoping 
Published: June 2021

Abstract
Background
Coronary artery lesions (CALs) are the most severe complication of Kawasaki disease (KD). Approximately 9–20% of the patients with KD develop CAL despite receiving regular treatment (intravenous immunoglobulin [IVIG] and aspirin). Some patients develop coronary aneurysms, leading to coronary artery stenosis or thrombosis, resulting in ischaemic heart disease and significantly affect the patients’ lives. The purpose of this study was to investigate the factors associated with the duration of CAL in patients with KD.

Methods
The data of 464 patients with KD and CAL admitted to the Children’s Heart Centre, The Second Affiliated Hospital and Yuying Children’s Hospital from 2010 to 2018 were retrospectively analysed. Demographic and clinical information and echocardiographic follow-up data were collected. Kaplan–Meier curves were used to estimate the overall CAL duration, and the log-rank test was used to compare statistical differences. Univariate and multivariate Cox regression models were used to identify variables related to the CAL duration.

Results
The median CAL duration was 46 days (95% confidence interval: 41–54 days). CALs were observed in 61.5, 41.5, 33.3, 22.3, 10.3, and 7.7% of the patients at 1 month, 2 months, 3 months, 6 months, 1 year, and 2 years after the onset of KD, respectively. Univariate Cox regression model showed that sex (p = 0.016), rash symptoms (p = 0.035), delayed IVIG treatment (p = 0.022), CAL type (p < 0.001), degree of CAL (p < 0.001), white blood cell count before IVIG treatment (p = 0.019), and platelet count after IVIG treatment (p = 0.003) were statistically significant factors associated with the overall CAL duration. Multivariable Cox regression showed that delayed IVIG treatment (p = 0.020), multiple dilatations (p < 0.001), a greater degree of dilatation (p < 0.001), and higher platelet count after IVIG treatment (p = 0.007) were positively related to CAL duration.

Conclusions
CAL duration was affected by delayed IVIG treatment, type of CAL, degree of CAL, and platelet count after IVIG treatment. These factors should be monitored carefully during the follow-up and management of patients with KD and CAL.
Chinese women’s attitudes towards postpartum interventions to prevent type 2 diabetes after gestational diabetes: a semi-structured qualitative study
Authors: Shang Jie , Henry Amanda , Zhang Puhong , Chen Huan , Thompson Kelly , Wang Xiaodong , Liu Na , Zhang Jiani , Liu Yan , Jin Jianbo , Pan Xiongfei , Yang Xue , Hirst Jane E. 
Published: June 2021

Abstract
Background
Gestational diabetes (GDM) is a global problem affecting millions of pregnant women, including in mainland China. These women are at high risk of Type II diabetes (T2DM). Cost-effective and clinically effective interventions are needed. We aimed to explore Chinese women’s perspectives, concerns and motivations towards participation in early postpartum interventions and/or research to prevent the development of T2DM after a GDM-affected pregnancy.

Methods
We conducted a qualitative study in two hospitals in Chengdu, Southwest China. Face-to-face semi-structured interviews were conducted with 20 women with recent experience of GDM: 16 postpartum women and 4 pregnant women. Women were asked about their attitudes towards postpartum screening for type 2 diabetes, lifestyle interventions, mHealth delivered interventions and pharmacologic interventions (specifically metformin). An inductive approach to analysis was used. Interviews were recorded, transcribed, and coded using NVivo 12 Pro.

Results
Most women held positive attitudes towards participating in T2DM screening, and were willing to participate in postpartum interventions to prevent T2DM through lifestyle change or mHealth interventions. Women were less likely to agree to pharmacological intervention, unless they had family members with diabetes or needed medication themselves during pregnancy. We identified seven domains influencing women’s attitudes towards future interventions: (1) experiences with the health system during pregnancy; (2) living in an enabling environment; (3) the experience of T2DM in family members; (4) knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions, and (7) lifestyle constraints. Those with more severe GDM, an enabling environment and health knowledge, and with experience of T2DM in family members expressed more favourable views of postpartum interventions and research participation to prevent T2DM after GDM. Those who perceived themselves as having mild GDM and those with time/lifestyle constraints were less likely to participate.

Conclusions
Women with experiences of GDM in Chengdu are generally willing to participate in early postpartum interventions and/or research to reduce their risk of T2DM, with a preference for non-drug, mHealth based interventions, integrating lifestyle change strategies, blood glucose monitoring, postpartum recovery and mental health.
Efficient translation of Eggplant mottled dwarf nucleorhabdovirus N and X genes requires both 5′ and 3′ UTRs
Authors: Babaei Ghobad , Massah Amir , Koohi Habibi Mina 
Published: June 2021

Abstract
Background
Circularization of RNA mediated by association of translation factors and RNA elements in 5′ and 3′ UTRs is a common feature for translation control in eukaryotes. There is no information about translation in plant rhabdoviruses and little information is known in animal rhabdoviruses.

Methods
The role of 5′ and 3′ UTRs in two genes of EMDV in translation were studied using luciferase constructs and RNA structures of these sequences were analyzed by SHAPE and Inline probing.

Results
We have found that efficient translation of N and X mRNAs of nucleorhabdovirus Eggplant mottled dwarf virus (EMDV) requires elements present in both 5′ and 3′ UTRs. Luciferase reporter constructs containing precise 5′ and 3′ UTRs of the N and X genes had substantially higher translational activity compared with constructs containing only the 5′ or 3′ UTR. The 3′UTR of carmovirus Turnip crinkle virus, which contains a well-characterized cap-independent translation enhancer, was unable to complement the lack of EMDV 3′ UTR. Addition of cap analog to luciferase constructs containing the UTRs of the N gene did not restore translation, and translation of the reporter construct in the absence of the 5′ cap was higher than the capped construct. No RNA-RNA interactions between 5′ and 3′ UTRs were detected by EMSA or in-line cleavage structural assays. Deletion of 11 nucleotides from the 3′ terminus negated the synergistic activity of the 3′UTR.

Conclusions
The results with RNA-RNA interaction suggesting that translational synergy between the UTRs may utilize alternative means. Mutation analysis in 3′UTR suggesting that the polyadenylation signal sequence contained in this location may play a critical role in translation.
Hybrid emergency rooms reduce the requirement of blood transfusion in patients with severe trauma
Authors: Watanabe Hiroaki , Matsumoto Ryo , Kuramoto Shunsuke , Muronoi Tomohiro , Oka Kazuyuki , Shimojo Yoshihide , Kidani Akihiko , Hira Eiji , Kawamura Toshihiko 
Published: June 2021

AbstractBackgroundA hybrid emergency room (ER) is defined as an emergency unit with four functions—performing resuscitation, computed tomography (CT), surgery, and angiography. However, the safety and efficacy of performing CT in a hybrid ER are unclear in primary surveys. Therefore, this study aimed to evaluate the safety and clinical effects of hybrid ERs.MethodsThis retrospective observational study used data from the Shimane University Hospital Trauma Database from January 2016 to February 2019. Hospitalized patients with severe trauma and an injury severity score of ≥ 16 were divided into the non-hybrid ER group (n = 134) and the hybrid ER group (n = 145). The time from arrival to CT and interventions and the number of in-hospital survivors, preventable trauma deaths (PTD), and unexpected survivors (US) were assessed in both groups. Further, the amount of blood transfused was compared between the groups using propensity score matching.ResultsThe time from arrival to CT and interventions was significantly reduced in the hybrid ER group compared to that in the non-hybrid ER group (25 vs. 6 min;p< 0.0001 and 101 vs. 41 min;p= 0.0007, respectively). There was no significant difference in the rate of in-hospital survivors (96.9% vs. 96.3%; p = 0.770), PTD (0% vs. 0%), and US (9.0 vs. 6.2%; p = 0.497) between the groups. The amount of blood transfused was significantly lower in the hybrid ER group than in the non-hybrid ER group (whole blood 14 vs. 8,p= 0.004; red blood cell 6 vs. 2,p= 0.012; fresh frozen plasma 9 vs. 6,p= 0.021). This difference was maintained after propensity score matching (whole blood 28 [10–54] vs. 6 [4–16.5],p= 0.015; RBC 8 [2.75–26.5] vs. 2 [0–8.5],p= 0.020, 18 [5.5–27] vs. 6 [3.5–7.5],p= 0.057).ConclusionsThe study results suggest that trauma treatment in a hybrid ER is as safe as conventional treatment performed in a non-hybrid ER. Further, hybrid ERs, which can reduce the time for trauma surveys and treatment, do not require patient transfer and can reduce the amount of blood transfused during resuscitation.
A novel retractor-assisted closed reduction combined with percutaneous pinning fixation for the treatment of elderly distal radius fractures: a retrospective cohort study
Authors: Zhao Bin , Zhao Wenqian , Assan Isaac , Li Zhenji , Bi Rongxiu 
Published: June 2021

Abstract
Background
Percutaneous pinning fixation (PCP) has been used for the treatment of distal radius fractures for decades, especially in the elderly with fragile soft tissue. However, achieving and maintaining a sound anatomic reduction before PCP is difficult if we use the manipulative reduction method alone. Our study innovatively applied the Steinmann pin retractor for closed reduction combined with PCP, to provide a new protocol for the treatment of distal radius fractures.

Methods
From March 2017 to July 2018, 49 patients out of 57 that met the inclusion criteria but not the exclusion criteria were included in our retrospective cohort study. Sixteen patients were treated with Steinmann pin retractor-assisted closed reduction combined with PCP (S-PCP), and 19 patients were treated with the manipulative reduction combined with PCP (M-PCP), and 14 patients were treated with the manipulative reduction combined with cast splint (M-C). All these patients received a positive postoperative radiological and clinical evaluation.

Results
All the patients were followed up for a minimum of 2 years. The radiological parameters in each group improved significantly postoperative (posttreatment). In the S-PCP group, the values of radial height (postoperative, 13.33±1.74 mm; the first follow-up, 13.27±1.81mm; last follow-up, 13.16±1.76mm) and ulnar variance (postoperative, −0.10±1.29mm; the first follow-up, −0.05±1.27mm; last follow-up, −0.12±1.09mm) significantly improved as compared to the M-PCP and M-C groups. While the patients in the M-C group experienced significant re-displacement at the first and last follow-ups, in the S-PCP group, the range of wrist motion including extension (89.94±5.21%), radial deviation (90.69±6.01%), and supination (90.25±5.87%); ulnar deviation (89.81±5.82%) and QuickDASH score (2.70±3.64); and grip strength (92.50±5.59%), pronation (90.50±6.04%), and modified Mayo wrist score (90.94±4.17, the excellent rate reached up to 75%) also improved as compared to the M-PCP group, M-C group, or both groups at the last follow-up.

Conclusion
S-PCP improves fracture reduction and wrist function and can serve as an effective method for A2(AO/OTA) and A3 type of distal radius fractures in the elderly with limited dorsal comminution, including intra-articular fractures with displacement less than 2mm.
Pharmacological rescue of cognitive function in a mouse model of chemobrain
Authors: Nguyen Lien D. , Fischer Tom T. , Ehrlich Barbara E. 
Published: June 2021

Abstract
Background
After chemotherapy, many cancer survivors suffer from long-lasting cognitive impairment, colloquially known as “chemobrain.” However, the trajectories of cognitive changes and the underlying mechanisms remain unclear. We previously established paclitaxel-induced inositol trisphosphate receptor (InsP3R)-dependent calcium oscillations as a mechanism for peripheral neuropathy, which was prevented by lithium pretreatment. Here, we investigated if a similar mechanism also underlay paclitaxel-induced chemobrain.

Method
Mice were injected with 4 doses of 20 mg/kg paclitaxel every other day to induced cognitive impairment. Memory acquisition was assessed with the displaced object recognition test. The morphology of neurons in the prefrontal cortex and the hippocampus was analyzed using Golgi-Cox staining, followed by Sholl analyses. Changes in protein expression were measured by Western blot.

Results
Mice receiving paclitaxel showed impaired short-term spatial memory acquisition both acutely 5 days post injection and chronically 23 days post injection. Dendritic length and complexity were reduced in the hippocampus and the prefrontal cortex after paclitaxel injection. Concurrently, the expression of protein kinase C α (PKCα), an effector in the InsP3R pathway, was increased. Treatment with lithium before or shortly after paclitaxel injection rescued the behavioral, cellular, and molecular deficits observed. Similarly, memory and morphological deficits could be rescued by pretreatment with chelerythrine, a PKC inhibitor.

Conclusion
We establish the InsP3R calcium pathway and impaired neuronal morphology as mechanisms for paclitaxel-induced cognitive impairment. Our findings suggest lithium and PKC inhibitors as candidate agents for preventing chemotherapy-induced cognitive impairment.