bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compacting a synthetic yeast chromosome arm
Authors: Luo Zhouqing , Yu Kang , Xie Shangqian , Monti Marco , Schindler Daniel , Fang Yuan , Zhao Shijun , Liang Zhenzhen , Jiang Shuangying , Luan Meiwei , Xiao Chuanle , Cai Yizhi , Dai Junbiao 
Published: January 2021

AbstractBackgroundRedundancy is a common feature of genomes, presumably to ensure robust growth under different and changing conditions. Genome compaction, removing sequences nonessential for given conditions, provides a novel way to understand the core principles of life. The synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) system is a unique feature implanted in the synthetic yeast genome (Sc2.0), which is proposed as an effective tool for genome minimization. As the Sc2.0 project is nearing its completion, we have begun to explore the application of the SCRaMbLE system in genome compaction.ResultsWe develop a method termed SCRaMbLE-based genome compaction (SGC) and demonstrate that a synthetic chromosome arm (synXIIL) can be efficiently reduced. The pre-introduced episomal essential gene array significantly enhances the compacting ability of SGC, not only by enabling the deletion of nonessential genes located in essential gene containing loxPsym units but also by allowing more chromosomal sequences to be removed in a single SGC process. Further compaction is achieved through iterative SGC, revealing that at least 39 out of 65 nonessential genes in synXIIL can be removed collectively without affecting cell viability at 30 °C in rich medium. Approximately 40% of the synthetic sequence, encoding 28 genes, is found to be dispensable for cell growth at 30 °C in rich medium and several genes whose functions are needed under specified conditions are identified.ConclusionsWe develop iterative SGC with the aid of eArray as a generic yet effective tool to compact the synthetic yeast genome.
Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer
Authors: Oka Miho , Xu Liu , Suzuki Toshihiro , Yoshikawa Toshiaki , Sakamoto Hiromi , Uemura Hayato , Yoshizawa Akiyasu C. , Suzuki Yutaka , Nakatsura Tetsuya , Ishihama Yasushi , Suzuki Ayako , Seki Masahide 
Published: January 2021

Abstract
Background
Long-read sequencing of full-length cDNAs enables the detection of structures of aberrant splicing isoforms in cancer cells. These isoforms are occasionally translated, presented by HLA molecules, and recognized as neoantigens. This study used a long-read sequencer (MinION) to construct a comprehensive catalog of aberrant splicing isoforms in non-small-cell lung cancers, by which novel isoforms and potential neoantigens are identified.

Results
Full-length cDNA sequencing is performed using 22 cell lines, and a total of 2021 novel splicing isoforms are identified. The protein expression of some of these isoforms is then validated by proteome analysis. Ablations of a nonsense-mediated mRNA decay (NMD) factor, UPF1, and a splicing factor, SF3B1, are found to increase the proportion of aberrant transcripts. NetMHC evaluation of the binding affinities to each type of HLA molecule reveals that some of the isoforms potentially generate neoantigen candidates. We also identify aberrant splicing isoforms in seven non-small-cell lung cancer specimens. An enzyme-linked immune absorbent spot assay indicates that approximately half the peptide candidates have the potential to activate T cell responses through their interaction with HLA molecules. Finally, we estimate the number of isoforms in The Cancer Genome Atlas (TCGA) datasets by referring to the constructed catalog and found that disruption of NMD factors is significantly correlated with the number of splicing isoforms found in the TCGA-Lung Adenocarcinoma data collection.

Conclusions
Our results indicate that long-read sequencing of full-length cDNAs is essential for the precise identification of aberrant transcript structures in cancer cells.
Combined low-dose everolimus and low-dose tacrolimus after Alemtuzumab induction therapy: a randomized prospective trial in lung transplantation
Authors: Benazzo Alberto , Cho Ara , Nechay Anna , Schwarz Stefan , Frommlet Florian , Wekerle Thomas , Hoetzenecker Konrad , Jaksch Peter 
Published: January 2021

Abstract
Background
Long-term outcomes of lung transplantation are severely affected by comorbidities and development of chronic rejection. Among the comorbidities, kidney insufficiency is one of the most frequent and it is mainly caused by the cumulative effect of calcineurin inhibitors (CNIs). Currently, the most used immunosuppression protocols worldwide include induction therapy and a triple-drug maintenance immunosuppression, with one calcineurin inhibitor, one anti-proliferative drug, and steroids. Our center has pioneered the use of alemtuzumab as induction therapy, showing promising results in terms of short- and long-term outcomes. The use of alemtuzumab followed by a low-dose double drug maintenance immunosuppression, in fact, led to better kidney function along with excellent results in terms of acute rejection, chronic lung allograft dysfunction, and survival (Benazzo et al., PLoS One 14(1):e0210443, 2019). The hypothesis driving the proposed clinical trial is that de novo introduction of low-dose everolimus early after transplantation could further improve kidney function via a further reduction of tacrolimus. Based on evidences from kidney transplantation, moreover, alemtuzumab induction therapy followed by a low-dose everolimus and low-dose tacrolimus may have a permissive action on regulatory immune cells thus stimulating allograft acceptance.

Methods
A randomized prospective clinical trial has been set up to answer the research hypothesis. One hundred ten patients will be randomized in two groups. Treatment group will receive the new maintenance immunosuppression protocol based on low-dose tacrolimus and low-dose everolimus and the control group will receive our standard immunosuppression protocol. Both groups will receive alemtuzumab induction therapy. The primary endpoint of the study is to analyze the effect of the new low-dose immunosuppression protocol on kidney function in terms of eGFR change. The study will have a duration of 24 months from the time of randomization. Immunomodulatory status of the patients will be assessed with flow cytometry and gene expression analysis.

Discussion
For the first time in the field of lung transplantation, this trial proposes the combined use of significantly reduced tacrolimus and everolimus after alemtuzumab induction. The new protocol may have a twofold advantage: (1) further reduction of nephrotoxic tacrolimus and (2) permissive influence on regulatory cells development with further reduction of rejection episodes.

Trial registration
EUDRACT Nr 2018-001680-24. Registered on 15 May 2018
A randomised controlled trial comparing palate surgery at 6 months versus 12 months of age (the TOPS trial): a statistical analysis plan
Authors:   On behalf of the TOPS trial management group, Conroy Elizabeth J. , Cooper Rachael , Shaw William , Persson Christina , Willadsen Elisabeth , Munro Kevin J. , Williamson Paula R. , Semb Gunvor , Walsh Tanya , Gamble Carrol 
Published: January 2021

Abstract
Background
Cleft palate is among the most common birth abnormalities. The success of primary surgery in the early months of life is crucial for successful feeding, hearing, dental development, and facial growth. Over recent decades, age at palatal surgery in infancy has reduced. The Timing Of Primary Surgery for cleft palate (TOPS) trial aims to determine whether, in infants with cleft palate, it is better to perform primary surgery at age 6 or 12 months (corrected for gestational age).

Methods/design
The TOPS trial is an international, two-arm, parallel group, randomised controlled trial. The primary outcome is insufficient velopharyngeal function at 5 years of age. Secondary outcomes, measured at 12 months, 3 years, and 5 years of age, include measures of speech development, safety of the procedure, hearing level, middle ear function, dentofacial development, and growth. The analysis approaches for primary and secondary outcomes are described here, as are the descriptive statistics which will be reported. The TOPS protocol has been published previously.

Discussion
This paper provides details of the planned statistical analyses for the TOPS trial and will reduce the risk of outcome reporting bias and data-driven results.

Trial registration
ClinicalTrials.gov NCT00993551. Registered on 9 October 2009.
Plant nutrient quality impacts survival and reproductive fitness of the dengue vector Aedes aegypti
Authors: Nyasembe Vincent Odhiambo , Tchouassi David Poumo , Muturi Martha Njeri , Pirk Christian W. W. , Sole Catherine L. , Torto Baldwyn 
Published: January 2021

Abstract
Background
In a recent study using DNA barcoding, we identified the plants fed upon by four Afro-tropical mosquito species that vector dengue, malaria, and Rift Valley fever. Herein, we have expanded on this study by investigating the role of three of the plants, Pithecellobium dulce (Fabaceae), Leonotis nepetifolia (Lamiaceae), and Opuntia ficus-indica (Cactaceae), on the survival, fecundity, and egg viability of the dengue vector Aedes aegypti.

Methods
We tested these effects using females that received (i) an initial three rations of blood meals and (ii) no blood meal at all. Two controls were included: age-matched females fed on glucose solution with or without an initial blood meal and those fed exclusively on blood meals. Data were collected daily over a 30-day period. The amino acid contents of Ae. aegypti guts and their respective diets were detected by coupled liquid chromatography-mass spectrometry.

Results
Females fed on P. dulce and an exclusively blood meal diet had a shorter survival than those fed on glucose. On the other hand, females fed on L. nepetifolia survived longer than those fed exclusively on blood meals, whereas those fed on O. ficus-indica had the shortest survival time. With an initial blood meal, females fed on L. nepetifolia laid 1.6-fold more eggs while those fed on the other diets laid fewer eggs compared to those fed exclusively on blood meals. Hatching rates of the eggs laid varied with the diet. Mass spectroscopic analysis of gut contents of mosquitoes exposed to the different diets showed qualitative and quantitative differences in their amino acid levels.

Conclusion
Our findings highlight the central role of plant nutrients in the reproductive fitness of dengue vectors, which may impact their disease transmission potential.

Graphical Abstract
Kinetic analysis of dominant intraprostatic lesion of prostate cancer using quantitative dynamic [18F]DCFPyL-PET: comparison to [18F]fluorocholine-PET
Authors: Yang Dae-Myoung , Li Fiona , Bauman Glenn , Chin Joseph , Pautler Stephen , Moussa Madeleine , Rachinsky Irina , Valliant John , Lee Ting-Yim 
Published: January 2021

Abstract
Purpose
Identification of the dominant intraprostatic lesion(s) (DILs) can facilitate diagnosis and treatment by targeting biologically significant intra-prostatic foci. A PSMA ligand, [18F]DCFPyL (2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid), is better than choline-based [18F]FCH (fluorocholine) in detecting and localizing DIL because of higher tumour contrast, particularly when imaging is delayed to 1 h post-injection. The goal of this study was to investigate whether the different imaging performance of [18F]FCH and [18F]DCFPyL can be explained by their kinetic behaviour in prostate cancer (PCa) and to evaluate whether DIL can be accurately detected and localized using a short duration dynamic positron emission tomography (PET).

Methods
19 and 23 PCa patients were evaluated with dynamic [18F]DCFPyL and [18F]FCH PET, respectively. The dynamic imaging protocol with each tracer had a total imaging time of 22 min and consisted of multiple frames with acquisition times from 10 to 180 s. Tumour and benign tissue regions identified by sextant biopsy were compared using standardized uptake value (SUV) and tracer kinetic parameters from kinetic analysis of time-activity curves.

Results
For [18F]DCFPyL, logistic regression identified Ki and k4 as the optimal model to discriminate tumour from benign tissue (84.2% sensitivity and 94.7% specificity), while only SUV was predictive for [18F]FCH (82.6% sensitivity and 87.0% specificity). The higher k3 (binding) of [18F]FCH than [18F]DCFPyL explains why [18F]FCH SUV can differentiate tumour from benign tissue within minutes of injection. Superior [18F]DCFPyL tumour contrast was due to the higher k4/k3 (more rapid washout) in benign tissue compared to tumour tissue.

Conclusions
DIL was detected with good sensitivity and specificity using 22-min dynamic [18F]DCFPyL PET and avoids the need for delayed post-injection imaging timepoints. The dissimilar in vivo kinetic behaviour of [18F]DCFPyL and [18F]FCH could explain their different SUV images.
Clinical Trial Registration NCT04009174 (ClinicalTrials.gov).
Streptococci as the new dominant aetiological factors of mastitis in dairy cows in north-eastern Poland: analysis of the results obtained in 2013–2019
Authors: Kaczorek-Łukowska E. , Małaczewska J. , Wójcik R. , Duk K. , Blank A. , Siwicki A. K. 
Published: January 2021

AbstractThe objective of our study was to evaluate prevalence of selected bacterial and fungal pathogens of mastitis in dairy cattle in north-eastern Poland. Our study was conducted from 2013 to 2019 in 1,665 clinically and sub-clinically infected quarter milk samples (2013, n = 368; 2014, n = 350; 2015, n = 290; 2016, n = 170; 2017, n = 173; 2018, n = 224; and 2019, n = 90). The isolation and identification of the pathogens were performed in keeping with generally accepted microbiological procedures. In 2013, mastitis was most commonly caused by Staphylococcus aureus (24%), Streptococcus spp. (22%), Streptococcus agalactiae (12%) and coagulase-negative staphylococci (11%). In 2014, the most common pathogens were Streptococcus spp. (25%), Staphylococcus aureus (18%) and coagulase-negative staphylococci (10%); in 2015, 2016, 2017, 2018 and 2019, Streptococcus spp. (from 39–49%) were the most frequent strains isolated from the quarter milk samples. Other pathogens were isolated occasionally (below 15% in all years). In conclusion, the role of environmental bacteria has been gradually increasing in the Warmia Province. The importance of infectious pathogens has been decreasing, indicating the efficacy of the applied preventive programmes and a need for the development of new programmes targeting environmental pathogens.
Effectiveness of task-shifting for the detection of diabetic retinopathy in low- and middle-income countries: a rapid review protocol
Authors: Bascaran Covadonga , Mwangi Nyawira , D’Esposito Fabrizio , Gordon Iris , Ulloa Juan Alberto Lopez , Mdala Shaffi , Ramke Jacqueline , Evans Jennifer R. , Burton Matthew 
Published: January 2021

Abstract
Background
Diabetic retinopathy is the most common ocular complication of diabetes and a cause of vision loss in adults. Diabetic retinopathy screening leading to early identification of the disease followed by timely treatment, can prevent vision loss in people living with diabetes. A key barrier to the implementation of screening services in low- and middle-income countries is the low number of ophthalmologists per million population. Interventions that shift screening to non-ophthalmology cadres have been implemented in programmes in low- and middle-income countries and are routinely used in high-income countries. The aim of this rapid review is to summarise the published literature reporting the effectiveness of task-shifting interventions for the detection of diabetic retinopathy by non-ophthalmologists in low- and middle-income countries.

Methods
We will search MEDLINE, Embase, Global Health and Cochrane Register of Studies for studies reporting task-shifting interventions for diabetic retinopathy detection. The review will include studies published in the last 10 years in the English language. We will include any interventional or observational comparative study measuring outcomes in terms of participation or access to diabetic retinopathy detection services (uptake) and quality of diabetic retinopathy detection services (detection, severity, diagnostic accuracy). For included studies, cost-effectiveness of the task-shifting intervention will also be presented. Two reviewers will screen search results independently. The risk of bias assessment and data extraction will be carried out by one reviewer with verification of 10% of the papers by a second reviewer. The results will be synthesised narratively.

Discussion
Differences in health systems organization, structure and resources will determine the need and success of task-shifting interventions for DR screening. The review will examine how these interventions have been used and/or tested in LMICs. The results will be of interest to policy makers and programme managers tasked with designing and implementing services to prevent and manage diabetes and its complications in similar settings.

Systematic review registration
OSF: https://osf.io/dfhg6/.
Comparison of respiratory pathogen colonization and antimicrobial susceptibility in people with cystic fibrosis bronchiectasis versus non-cystic fibrosis bronchiectasis: a protocol for a systematic review
Authors: Verma Salony , Mathew Joseph L. , Ray Pallab 
Published: January 2021

Abstract
Background
Both cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis are characterized by permanent bronchial dilation, impaired mucociliary clearance, and development of chronic colonization and infection. Although the major airway microbiota in both CF and non-CF bronchiectasis may be similar, there are some differences in clinical and microbiologic features. There may also be differences in antibiotic susceptibility patterns between the CF and non-CF populations. Therefore, analysis and comparison of the microbiota and antibiotic susceptibility pattern in CF bronchiectasis versus non-CF bronchiectasis would help to improve the management of both conditions.

Methods
Two authors will independently search the electronic databases PubMed, EMBASE, the Cochrane Library, and LIVIVO, for studies reporting bacterial colonization of the respiratory tract in adults and children diagnosed with bronchiectasis in either CF or non-CF. We will include studies examining any respiratory tract specimen, using conventional bacterial culture or other specialized techniques such as molecular methods. We will also examine the antimicrobial susceptibility patterns in people with CF bronchiectasis versus non-CF bronchiectasis. The authors will independently assess the risk of bias in each included study using the Newcastle Ottawa Scale (NOS). We will present the data with descriptive statistics and provide pooled estimates of outcomes, wherever it is feasible to perform meta-analysis. Heterogeneity in studies will be explored by visual inspection of forest plots as well as using the Higgins and Thompson I2 method. We will contact the corresponding authors of studies where data is/are missing and try to obtain the missing data. We will undertake sensitivity analysis to explore the impact of study quality and subgroup analysis based on pre-set criteria. We will prepare a summary of findings’ table and assess the confidence in the evidence using the GRADE methodology.

Discussion
To date, there are no locally applicable evidence-based guidelines for antimicrobial treatment of non-CF bronchiectasis patients. In general, treatment is based on extrapolation of evidence in people with CF bronchiectasis. An insight into the microbiota and antimicrobial susceptibility patterns in the two conditions would facilitate appropriate rather than empiric antimicrobial therapy and hopefully reduce the burden of antimicrobial resistance created by rampant usage of antibiotics.

Systematic review registration
The protocol has been registered in PROSPERO on July 26, 2020 (PROSPERO registration number: CRD42020193859).
$L^{\infty }$ decay estimates of solutions of nonlinear parabolic equation
Authors: Wang Hui , Chen Caisheng 
Published: January 2021

AbstractIn this paper, we are interested in $L^{\infty }$

L
∞

decay estimates of weak solutions for the doubly nonlinear parabolic equation and the degenerate evolution m-Laplacian equation not in the divergence form. By a modified Moser’s technique we obtain $L^{\infty }$

L
∞

decay estimates of weak solutiona.
Current and near-term advances in Earth observation for ecological applications
Authors: Ustin Susan L. , Middleton Elizabeth M. 
Published: January 2021

AbstractThere is an unprecedented array of new satellite technologies with capabilities for advancing our understanding of ecological processes and the changing composition of the Earth’s biosphere at scales from local plots to the whole planet. We identified 48 instruments and 13 platforms with multiple instruments that are of broad interest to the environmental sciences that either collected data in the 2000s, were recently launched, or are planned for launch in this decade. We have restricted our review to instruments that primarily observe terrestrial landscapes or coastal margins and are available under free and open data policies. We focused on imagers that passively measure wavelengths in the reflected solar and emitted thermal spectrum. The suite of instruments we describe measure land surface characteristics, including land cover, but provide a more detailed monitoring of ecosystems, plant communities, and even some species then possible from historic sensors. The newer instruments have potential to greatly improve our understanding of ecosystem functional relationships among plant traits like leaf mass area (LMA), total nitrogen content, and leaf area index (LAI). They provide new information on physiological processes related to photosynthesis, transpiration and respiration, and stress detection, including capabilities to measure key plant and soil biophysical properties. These include canopy and soil temperature and emissivity, chlorophyll fluorescence, and biogeochemical contents like photosynthetic pigments (e.g., chlorophylls, carotenoids, and phycobiliproteins from cyanobacteria), water, cellulose, lignin, and nitrogen in foliar proteins. These data will enable us to quantify and characterize various soil properties such as iron content, several types of soil clays, organic matter, and other components. Most of these satellites are in low Earth orbit (LEO), but we include a few in geostationary orbit (GEO) because of their potential to measure plant physiological traits over diurnal periods, improving estimates of water and carbon budgets. We also include a few spaceborne active LiDAR and radar imagers designed for quantifying surface topography, changes in surface structure, and 3-dimensional canopy properties such as height, area, vertical profiles, and gap structure. We provide a description of each instrument and tables to summarize their characteristics. Lastly, we suggest instrument synergies that are likely to yield improved results when data are combined.