bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of individuals at high risk of chronic kidney disease during treatment with lithium for bipolar disorder
Authors: Hayes Joseph F. , Osborn David P. J. , Francis Emma , Ambler Gareth , Tomlinson Laurie A. , Boman Magnus , Wong Ian C. K. , Geddes John R. , Dalman Christina , Lewis Glyn 
Published: April 2021

Abstract
Background
Lithium is the most effective treatment in bipolar disorder. Its use is limited by concerns about risk of chronic kidney disease (CKD). We aimed to develop a model to predict risk of CKD following lithium treatment initiation, by identifying individuals with a high-risk trajectory of kidney function.

Methods
We used United Kingdom Clinical Practice Research Datalink (CPRD) electronic health records (EHRs) from 2000 to 2018. CPRD Aurum for prediction model development and CPRD Gold for external validation. We used elastic net regularised regression to generate a prediction model from potential features. We performed discrimination and calibration assessments in an external validation data set.
We included all patients aged ≥ 16 with bipolar disorder prescribed lithium. To be included patients had to have ≥ 1 year of follow-up before lithium initiation, ≥ 3 estimated glomerular filtration rate (eGFR) measures after lithium initiation (to be able to determine a trajectory) and a normal (≥ 60 mL/min/1.73 m2) eGFR at lithium initiation (baseline). In the Aurum development cohort, 1609 fulfilled these criteria. The Gold external validation cohort included 934 patients.
We included 44 potential baseline features in the prediction model, including sociodemographic, mental and physical health and drug treatment characteristics. We compared a full model with the 3-variable 5-year kidney failure risk equation (KFRE) and a 3-variable elastic net model.
We used group-based trajectory modelling to identify latent trajectory groups for eGFR. We were interested in the group with deteriorating kidney function (the high-risk group).

Results
The high risk of deteriorating eGFR group included 191 (11.87%) of the Aurum cohort and 137 (14.67%) of the Gold cohort. Of these, 168 (87.96%) and 117 (85.40%) respectively developed CKD 3a or more severe during follow-up. The model, developed in Aurum, had a ROC area of 0.879 (95%CI 0.853–0.904) in the Gold external validation data set. At the empirical optimal cut-point defined in the development dataset, the model had a sensitivity of 0.91 (95%CI 0.84–0.97) and a specificity of 0.74 (95% CI 0.67–0.82). However, a 3-variable elastic net model (including only age, sex and baseline eGFR) performed similarly well (ROC area 0.888; 95%CI 0.864–0.912), as did the KFRE (ROC area 0.870; 95%CI 0.841–0.898).

Conclusions
Individuals at high risk of a poor eGFR trajectory can be identified before initiation of lithium treatment by a simple equation including age, sex and baseline eGFR. Risk was increased in individuals who were younger at commencement of lithium, female and had a lower baseline eGFR. We did not identify strong predicters of eGFR decline specific to lithium-treated patients. Notably, lithium duration and toxicity were not associated with high-risk trajectory.
Gene expression and DNA methylation analyses suggest that two immune related genes are prognostic factors of colorectal cancer
Authors: Xing Xiao-Liang , Yao Zhi-Yong , Xing Chaoqun , Huang Zhi , Peng Jing , Liu Yuan-Wu 
Published: April 2021

Abstract
Background
Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC.

Methods
In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model.

Results
Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers.

Conclusion
This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.
Nitric oxide donor sodium nitroprusside-induced transcriptional changes and hypocrellin biosynthesis of Shiraia sp. S9
Authors: Ma Yan Jun , Li Xin Ping , Wang Yue , Wang Jian Wen 
Published: April 2021

AbstractBackgroundNitric oxide (NO) is a ubiquitous signaling mediator in various physiological processes. However, there are less reports concerning the effects of NO on fungal secondary metabolites. Hypocrellins are effective anticancer photodynamic therapy (PDT) agents from fungal perylenequinone pigments ofShiraia. NO donor sodium nitroprusside (SNP) was used as a chemical elicitor to promote hypocrellin biosynthesis inShiraiamycelium cultures.ResultsSNP application at 0.01–0.20 mM was found to stimulate significantly fungal production of perylenequinones including hypocrellin A (HA) and elsinochrome A (EA). SNP application could not only enhance HA content by 178.96% in mycelia, but also stimulate its efflux to the medium. After 4 days of SNP application at 0.02 mM, the highest total production (110.34 mg/L) of HA was achieved without any growth suppression. SNP released NO in mycelia and acted as a pro-oxidant, thereby up-regulating the gene expression and activity of reactive oxygen species (ROS) generating NADPH oxidase (NOX) and antioxidant enzymes, leading to the increased levels of superoxide anion (O2−) and hydrogen peroxide (H2O2). Gene ontology (GO) analysis revealed that SNP treatment could up-regulate biosynthetic genes for hypocrellins and activate the transporter protein major facilitator superfamily (MFS) for the exudation. Moreover, SNP treatment increased the proportion of total unsaturated fatty acids in the hypha membranes and enhanced membrane permeability. Our results indicated both cellular biosynthesis of HA and its secretion could contribute to HA production induced by SNP.ConclusionsThe results of this study provide a valuable strategy for large-scale hypocrellin production and can facilitate further understanding and exploration of NO signaling in the biosynthesis of the important fungal metabolites.
The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure
Authors: He Aihua , Zou Yangyun , Wan Cheng , Zhao Jing , Zhang Qiong , Yao Zhongyuan , Tian Fen , Wu Hong , Huang Xi , Fu Jing , Hu Chunxu , Sun Yue , Xiao Lan , Yang Tianli , Hou Zhaojuan , Dong Xin , Lu Sijia , Li Yanping 
Published: April 2021

AbstractBackgroundWindow of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF.MethodsThis was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group.ResultsThe rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830;P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718;P = 0.111) when transferring blastocysts.ConclusionsThe rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET.Trial registrationChinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017,http://www.chictr.org.cn/index.aspx
The gut microbiota is associated with the small intestinal paracellular permeability and the development of the immune system in healthy children during the first two years of life
Authors: Kaczmarczyk Mariusz , Löber Ulrike , Adamek Karolina , Węgrzyn Dagmara , Skonieczna-Żydecka Karolina , Malinowski Damian , Łoniewski Igor , Markó Lajos , Ulas Thomas , Forslund Sofia K. , Łoniewska Beata 
Published: April 2021

AbstractBackgroundThe intestinal barrier plays an important role in the defense against infections, and nutritional, endocrine, and immune functions. The gut microbiota playing an important role in development of the gastrointestinal tract can impact intestinal permeability and immunity during early life, but data concerning this problem are scarce.MethodsWe analyzed the microbiota in fecal samples (101 samples in total) collected longitudinally over 24 months from 21 newborns to investigate whether the markers of small intestinal paracellular permeability (zonulin) and immune system development (calprotectin) are linked to the gut microbiota. The results were validated using data from an independent cohort that included the calprotectin and gut microbiota in children during the first year of life.ResultsZonulin levels tended to increase for up to 6 months after childbirth and stabilize thereafter remaining at a high level while calprotectin concentration was high after childbirth and began to decline from 6 months of life. The gut microbiota composition and the related metabolic potentials changed during the first 2 years of life and were correlated with zonulin and calprotectin levels. Faecal calprotectin correlated inversely with alpha diversity (Shannon index, r = − 0.30, FDR P (Q) = 0.039). It also correlated with seven taxa; i.a. negatively with Ruminococcaceae (r = − 0.34, Q = 0.046), and Clostridiales (r = − 0.34, Q = 0.048) and positively withStaphylococcus(r = 0.38, Q = 0.023) and Staphylococcaceae (r = 0.35, Q = 0.04), whereas zonulin correlated with 19 taxa; i.a. with Bacillales (r = − 0.52, Q = 0.0004), Clostridiales (r = 0.48, Q = 0.001) and theRuminococcus(torquesgroup) (r = 0.40, Q = 0.026). When time intervals were considered only changes in abundance of theRuminococcus(torquesgroup) were associated with changes in calprotectin (β = 2.94, SE = 0.8, Q = 0.015). The dynamics of stool calprotectin was negatively associated with changes in two MetaCyc pathways: pyruvate fermentation to butanoate (β = − 4.54, SE = 1.08, Q = 0.028) andClostridium acetobutylicumfermentation (β = − 4.48, SE = 1.16, Q = 0.026).ConclusionsThe small intestinal paracellular permeability, immune system-related markers and gut microbiota change dynamically during the first 2 years of life. TheRuminococcus(torquesgroup) seems to be especially involved in controlling paracellular permeability.Staphylococcus,Staphylococcaceae, Ruminococcaceae, and Clostridiales, may be potential biomarkers of the immune system. Despite observed correlations their clear causation and health consequences were not proven. Mechanistic studies are required.Graphic abstract
Effects of tree species diversity and stand structure on carbon stocks of homestead forests in Maheshkhali Island, Southern Bangladesh
Authors: Baul Tarit Kumar , Chakraborty Avinanda , Nandi Rajasree , Mohiuddin Mohammed , Kilpeläinen Antti , Sultana Taslima 
Published: April 2021

AbstractBackgroundThe homestead forests of Bangladesh occupy 0.27 million hectares (10% of the total forested area) and have potential to store carbon (C) and conserve biodiversity. Small scale forestry practices, however, are lacking reliable estimation of C stocks and tree species diversity. This may hinder successful implementation of REDD + and similar mechanisms as they concentrate on large-scale forests. This study aimed to estimate the above- and below-ground carbon stocks in homestead forests of Maheshkhali Island in Bangladesh and how tree species diversity and stand structural variation affect these C stocks. We randomly surveyed a total of 239 homestead forests in the hillside, beachside, and inland in 2019.ResultsTree biomass C stocks were 48–67% greater in the inland and hillside forests than in the beachside due to significantly greater stand density, basal area, tree diameter. In total we found 52 tree species, but most abundant species in the inland and hillside forests,Mangifera indica,Samanea saman, andArtocarpus heterophyllusstored the most C in tree biomass. Greater tree species richness and diversity index in the inland and hillside forests indicated greater above- and below-ground tree biomass C stocks. An increase in tree species richness and diversity index by one unit was found to increase the tree biomass C stock by 22 and 30 Mg C ha−1, respectively. The total soil C stock was also affected by tree species diversity, stand density, and their interaction with soil properties. Total soil C stocks were greatest (51 Mg ha−1) in the inland forests, having also the greatest stand density and tree species richness. C stock in soil surface was greatest in the hillside forests due to the greatest litterfall, but the average share of litterfall from the total biomass C was only 0.1%.ConclusionsHomestead forest ecosystems could store 96 Mg C ha−1in total, which can contribute to climate change mitigation by generating C credits for small-scale homestead forests owners. Above- and below-ground tree biomass C stocks were found to correlate with tree species diversity, which may also contribute to biodiversity conservation in the REDD + in Bangladesh and countries alike.
Simultaneous development of COVID-19 pneumonia and pulmonary metastasis in a known case of chondrosarcoma: a case report
Authors: Rakhsha Afshin , Mahboubi-Fooladi Zahra , Jafari Anya 
Published: April 2021

Abstract
Background
The outbreak of coronavirus disease 2019 (COVID-19) started in December 2020, and is a global problem now. There are several sets of established data regarding computed tomography (CT) findings in COVID-19 pneumonia with many differential diagnoses. During the early days of the pandemic, there was little data regarding lung CT features of COVID-19 in a cancer patient. In this paper, we described a rare case of simultaneous presentation of COVID-19 with pulmonary metastasis.

Case presentation
A Persian patient with a history of chondrosarcoma presented to our clinic during the COVID-19 pandemic with a new-onset cough. He had experienced no recurrence during previous follow-up visits. Chest CT scan revealed numerous bilateral small peripheral and perilymphatic pulmonary nodules, unilateral ground-glass patch, and nodular interlobular septal thickening. Biopsy of the pulmonary nodules established pulmonary metastasis of chondrosarcoma origin, and pharyngeal reverse transcription polymerase chain reaction (RT-PCR) was positive for COVID-19.

Conclusion
Pulmonary metastasis should be considered as a differential diagnosis of COVID-19 features in cancer patients in the pandemic era.
Trajectory planning in UAV emergency networks with potential underlaying D2D communication based on K-means
Authors: Zhang Shuo , Shi Shuo , Feng Tianming , Gu Xuemai 
Published: April 2021

AbstractAt present, unmanned aerial vehicles (UAVs) have been widely used in communication systems, and the fifth-generation wireless system (5G) has further promoted the vigorous development of them. The trajectory planning of UAV is an important factor that affects the timeliness and completion of missions, especially in scenarios such as emergency communications and post-disaster rescue. In this paper, we consider an emergency communication network where a UAV aims to achieve complete coverage of potential underlaying device-to-device (D2D) users. Trajectory planning issues are grouped into clustering and supplementary phases for optimization. Aiming at trajectory length and sum throughput, two trajectory planning algorithms based on K-means are proposed, respectively. In addition, in order to balance sum throughput with trajectory length, we present a joint evaluation index. Then relying on this index, a third trajectory optimization algorithm is further proposed. Simulation results show the validity of the proposed algorithms which have advantages over the well-known benchmark scheme in terms of trajectory length and sum throughput.
Chronic disease multimorbidity among the Canadian population: prevalence and associated lifestyle factors
Authors: Geda Nigatu Regassa , Janzen Bonnie , Pahwa Punam 
Published: April 2021

AbstractBackgroundChronic diseases is increasingly becoming one of the most pressing public health concerns in most part of the world, including the Canadian population. The purpose of this study was to estimate the prevalence of multimorbidity in the general population based on 14 major chronic diseases and examine associations with lifestyle/behavioral factors.MethodsThe data source was the 2015–2016 Canadian Community Health Survey (CCHS). The CCHS is a cross sectional, complex multi-stage survey based on information collected from 109,659 participants aged 12+, covering all provinces and territories. Multimorbidity was defined as the co-occurrence of two or more chronic diseases within a person. Multiple logistic regression was used to examine the key determinants of multimorbidity.ResultsThe prevalence of multimorbidity was 33 %. Adjusting for sociodemographic variables, there was an increased odd of multimorbidity for those having a sedentary lifestyle (AOR = 1.06; CI:1.01–1.11) and being obese (AOR = 1.37; CI:1.32–1.43) or overweight (AOR = 2.65; CI: 2.54–2.76). There were two statistically significant interactions, between sex and smoking, and between immigration status and alcohol intake. Smoking was more strongly associated with multimorbidity in females than males. The association between alcohol intake and multimorbidity was also dependent upon immigration status.ConclusionsGiven the high prevalence of multimorbidity among the general Canadian population, policy makers and service providers should give more attention to the behavioral/lifestyle factors which significantly predicted multimorbidity. Policy and program efforts that promote a healthy lifestyle should be a priority.
EU FP7 research funding for an orphan drug (Orfadin®) and vaccine (Hep C) development: a success and a failure?
Authors: Schmidt L. , Sehic O. , Wild C. 
Published: April 2021

Abstract
Background
We considered the extent of the contribution of publicly funded research to the late-stage clinical development of pharmaceuticals and medicinal products, based on the European Commission (EC) FP7 research funding programme. Using two EC FP7-HEALTH case study examples—representing two types of outcomes—we then estimated wider public and charitable research funding contributions.

Methods
Using the publicly available database of FP7-HEALTH funded projects, we identified awards relating to late-stage clinical development according to the systematic application of inclusion and exclusion criteria, classified them according to product type and clinical indication, and calculated total EC funding amounts. We then identified two case studies representing extreme outcomes: failure to proceed with the product (hepatitis C vaccine) and successful market authorisation (Orfadin® for alkaptonuria). Total public and philanthropic research funding contributions to these products were then estimated using publicly available information on funding.

Results
12.3% (120/977) of all EC FP7-HEALTH awards related to the funding of late-stage clinical research, totalling € 686,871,399. Pharmaceutical products and vaccines together accounted for 84% of these late-stage clinical development research awards and 70% of its funding. The hepatitis C vaccine received total European Community (FP7 and its predecessor, EC Framework VI) funding of €13,183,813; total public and charitable research funding for this product development was estimated at € 77,060,102. The industry sponsor does not consider further development of this product viable; this now represents public risk investment. FP7 funding for the late-stage development of Orfadin® for alkaptonuria was so important that the trials it funded formed the basis for market authorisation, but it is not clear whether the price of the treatment (over €20,000 per patient per year) adequately reflects the substantial public funding contribution.

Conclusions
Public and charitable research funding plays an essential role, not just in early stage basic research, but also in the late-stage clinical development of products prior to market authorisation. In addition, it provides risk capital for failed products. Within this context, we consider further discussions about a public return on investment and its reflection in pricing policies and decisions justified.