bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of regional sea-level rise acceleration for the North Sea
Authors: Steffelbauer David B , Riva Riccardo E M , Timmermans Jos S , Kwakkel Jan H , Bakker Mark 
Published: June 2022

Abstract
Global mean sea-level rise (SLR) has accelerated since 1900 from less than 2 mm yr−1 during most of the century to more than 3 mm yr−1 since 1993. Decision-makers in coastal countries, however, require information on SLR at the regional scale, where detection of an acceleration in SLR is difficult, because the long-term sea-level signal is obscured by large inter-annual variations with multi-year trends that are easily one order of magnitude larger than global mean values. Here, we developed a time series approach to determine whether regional SLR is accelerating based on tide gauge data. We applied the approach to eight 100-year records in the southern North Sea and detected, for the first time, a common breakpoint in the early 1990s. The mean SLR rate at the eight stations increases from 1.7 ± 0.3 mm yr−1 before the breakpoint to 2.7 ± 0.4 mm yr−1 after the breakpoint (95% confidence interval), which is unprecedented in the regional instrumental record. These findings are robust provided that the record starts before 1970 and ends after 2015. Our method may be applied to any coastal region with tidal records spanning at least 40 years, which means that vulnerable coastal communities still have time to accumulate the required time series as a basis for adaptation decisions in the second half of this century.
Genotypic variation rather than ploidy level determines functional trait expression in a foundation tree species in the presence and absence of environmental stress
Authors: Eisenring Michael , Lindroth Richard L , Flansburg Amy , Giezendanner Noreen , Mock Karen E , Kruger Eric L 
Published: June 2022

Abstract

Background and Aims
At the population level, genetic diversity is a key determinant of a tree species’ capacity to cope with stress. However, little is known about the relative importance of the different components of genetic diversity for tree stress responses. We compared how two sources of genetic diversity, genotype and cytotype (i.e. differences in ploidy levels), influence growth, phytochemical and physiological traits of Populus tremuloides in the presence and absence of environmental stress.

Methods
In a series of field studies, we first assessed variation in traits across diploid and triploid aspen genotypes from Utah and Wisconsin under non-stressed conditions. In two follow-up experiments, we exposed diploid and triploid aspen genotypes from Wisconsin to individual and interactive drought stress and defoliation treatments and quantified trait variations under stress.

Key Results
We found that (1) tree growth and associated traits did not differ significantly between ploidy levels under non-stressed conditions. Instead, variation in tree growth and most other traits was driven by genotypic and population differences. (2) Genotypic differences were critical for explaining variation of most functional traits and their responses to stress. (3) Ploidy level played a subtle role in shaping traits and trait stress responses, as its influence was typically obscured by genotypic differences. (4) As an exception to the third conclusion, we showed that triploid trees expressed 17 % higher foliar defence (tremulacin) levels, 11 % higher photosynthesis levels and 23 % higher rubisco activity under well-watered conditions. Moreover, triploid trees displayed greater drought resilience than diploids as they produced 35 % more new tissue than diploids when recovering from drought stress.

Conclusion
Although ploidy level can strongly influence the ecology of tree species, those effects may be relatively small in contrast to the effects of genotypic variation in highly diverse species.
Trying out a million genes to find the perfect pair withRTIST
Authors: Zhelezov Gleb , Degnan James H 
Published: June 2022

AbstractMotivationConsensus methods can be used for reconstructing a species tree from several gene trees, which exhibit incompatible topologies due to incomplete lineage sorting. Motivated by the fact that there are no anomalous rooted gene trees with three taxa and no anomalous unrooted gene trees with four taxa in the multispecies coalescent model, several contemporary methods form the gene tree consensus by finding the median tree with respect to the triplet or quartet distance—i.e. estimate the species tree as the tree which minimizes the sum of triplet or quartet distances to the input gene trees. These methods reformulate the solution to the consensus problem as the solution to a recursively solved dynamic programming (DP) problem. We present an iterative, easily parallelizable approach to finding the exact median triplet tree and implement it as an open source software package that can also find suboptimal consensus trees within a specified triplet distance to the gene trees. The most time-consuming step for methods of this type is the creation of a weights array for all possible subtree bipartitions. By grouping the relevant calculations and array update operations of different bipartitions of the same subtree together, this implementation finds the exact median tree of many gene trees faster than comparable methods, has better scaling properties with respect to the number of gene trees and has a smaller memory footprint.ResultsRTIST (Rooted Triple Inference of Species Trees) finds the exact median triplet tree of a set of gene trees. Its runtime and memory footprints scale better than existing algorithms. RTIST can resolve all the non-unique median trees, as well as sub-optimal consensus trees within a user-specified triplet distance to the median. Although it is limited in the number of taxa (≤20), its runtime changes little when the number of gene trees is changed by several orders of magnitude.Availability and implementationRTIST is written in C and Python. It is freely available at https://github.com/glebzhelezov/rtist
MIO: microRNA target analysis system for immuno-oncology
Authors: Monfort-Lanzas Pablo , Gronauer Raphael , Madersbacher Leonie , Schatz Christoph , Rieder Dietmar , Hackl Hubert 
Published: June 2022

AbstractSummaryMicroRNAs have been shown to be able to modulate the tumor microenvironment and the immune response and hence could be interesting biomarkers and therapeutic targets in immuno-oncology; however, dedicated analysis tools are missing. Here, we present a user-friendly web platform MIO and a Python toolkit miopy integrating various methods for visualization and analysis of provided or custom bulk microRNA and gene expression data. We include regularized regression and survival analysis and provide information of 40 microRNA target prediction tools as well as a collection of curated immune related gene and microRNA signatures and processed TCGA data including estimations of infiltrated immune cells and the immunophenoscore. The integration of several machine learning methods enables the selection of prognostic and predictive microRNAs and gene interaction network biomarkers.Availability and implementationhttps://mio.icbi.at, https://github.com/icbi-lab/mio and https://github.com/icbi-lab/miopy.Supplementary informationSupplementary data are available at Bioinformatics online.
Estimation of cancer cell fractions and clone trees from multi-region sequencing of tumors
Authors: Zheng Lily , Niknafs Noushin , Wood Laura D , Karchin Rachel , Scharpf Robert B 
Published: June 2022

AbstractMotivationMulti-region sequencing of solid tumors can improve our understanding of intratumor subclonal diversity and the evolutionary history of mutational events. Due to uncertainty in clonal composition and the multitude of possible ancestral relationships between clones, elucidating the most probable relationships from bulk tumor sequencing poses statistical and computational challenges.ResultsWe developed a Bayesian hierarchical model called PICTograph to model uncertainty in assigning mutations to subclones, to enable posterior distributions of cancer cell fractions (CCFs) and to visualize the most probable ancestral relationships between subclones. Compared with available methods, PICTograph provided more consistent and accurate estimates of CCFs and improved tree inference over a range of simulated clonal diversity. Application of PICTograph to multi-region whole-exome sequencing of tumors from individuals with pancreatic cancer precursor lesions confirmed known early-occurring mutations and indicated substantial molecular diversity, including 6–12 distinct subclones and intra-sample mixing of subclones. Using ensemble-based visualizations, we highlight highly probable evolutionary relationships recovered in multiple models. PICTograph provides a useful approximation to evolutionary inference from cross-sectional multi-region sequencing, particularly for complex cases.Availability and implementationhttps://github.com/KarchinLab/pictograph. The data underlying this article will be shared on reasonable request to the corresponding author.Supplementary informationSupplementary data are available at Bioinformatics online.
VOC-alarm: mutation-based prediction of SARS-CoV-2 variants of concern
Authors: Zhao Hongyu , Han Kun , Gao Chao , Madhira Vithal , Topaloglu Umit , Lu Yong , Jin Guangxu 
Published: June 2022

ABSTRACTSummaryMutation is the key for a variant of concern (VOC) to overcome selective pressures, but this process is still unclear. Understanding the association of the mutational process with VOCs is an unmet need. Motivation: Here, we developed VOC-alarm, a method to predict VOCs and their caused COVID surges, using mutations of about 5.7 million SARS-CoV-2 complete sequences. We found that VOCs rely on lineage-level entropy value of mutation numbers to compete with other variants, suggestive of the importance of population-level mutations in the virus evolution. Thus, we hypothesized that VOCs are a result of a mutational process across the globe. Results: Analyzing the mutations from January 2020 to December 2021, we simulated the mutational process by estimating the pace of evolution, and thus divided the time period, January 2020—March 2022, into eight stages. We predicted Alpha, Delta, Delta Plus (AY.4.2) and Omicron (B.1.1.529) by their mutational entropy values in the Stages I, III, V and VII with accelerated paces, respectively. In late November 2021, VOC-alarm alerted that Omicron strongly competed with Delta and Delta plus to become a highly transmissible variant. Using simulated data, VOC-alarm also predicted that Omicron could lead to another COVID surge from January 2022 to March 2022.Availability and implementationOur software implementation is available at https://github.com/guangxujin/VOC-alarm.Supplementary informationSupplementary data are available at Bioinformatics online.
CNpare: matching DNA copy number profiles
Authors: Chaves-Urbano Blas , Hernando Barbara , Garcia Maria J , Macintyre Geoff 
Published: June 2022

AbstractSummarySelecting the optimal cancer cell line for an experiment can be challenging given the diversity of lines available. Here, we present CNpare, which identifies similar cell line models based on genome-wide DNA copy number.Availability and implementationCNpare is available as an R package at https://github.com/macintyrelab/CNpare. All analysis performed in the manuscript can be reproduced via the code found at https://github.com/macintyrelab/CNpare_analyses.Supplementary informationSupplementary data are available at Bioinformatics online.
gcFront: a tool for determining a Pareto front of growth-coupled cell factory designs
Authors: Legon Laurence , Corre Christophe , Bates Declan G , Mannan Ahmad A 
Published: June 2022

AbstractMotivationA widely applicable strategy to create cell factories is to knockout (KO) genes or reactions to redirect cell metabolism so that chemical synthesis is made obligatory when the cell grows at its maximum rate. Synthesis is thus growth-coupled, and the stronger the coupling the more deleterious any impediments in synthesis are to cell growth, making high producer phenotypes evolutionarily robust. Additionally, we desire that these strains grow and synthesize at high rates. Genome-scale metabolic models can be used to explore and identify KOs that growth-couple synthesis, but these are rare in an immense design space, making the search difficult and slow.ResultsTo address this multi-objective optimization problem, we developed a software tool named gcFront—using a genetic algorithm it explores KOs that maximize cell growth, product synthesis and coupling strength. Moreover, our measure of coupling strength facilitates the search so that gcFront not only finds a growth-coupled design in minutes but also outputs many alternative Pareto optimal designs from a single run—granting users flexibility in selecting designs to take to the lab.Availability and implementationgcFront, with documentation and a workable tutorial, is freely available at GitHub: https://github.com/lLegon/gcFront and archived at Zenodo, DOI: 10.5281/zenodo.5557755.Supplementary informationSupplementary data are available at Bioinformatics online.
Outcomes of bariatric surgery in elderly patients: A registry-based cohort study with 3-year follow-up
Authors: Iranmanesh P , Boudreau V , Anvari M 
Published: June 2022

Abstract

Objective
Elderly patients undergo bariatric surgery less frequently than younger patients. Short- and medium-term outcomes after bariatric surgery in the elderly population remain largely unknown. The objective of the present retrospective, registry-based cohort study was to compare short- and medium-term outcomes between patients &lt;65 and ≥65 years undergoing bariatric surgery, hypothesizing similar outcomes between groups.

Methods
In this retrospective, registry-based cohort study, the Ontario Bariatric Registry was used to compare data of patients &lt;65 and ≥65 years who underwent Roux-en-Y gastric bypass and sleeve gastrectomy between January 2010 and August 2019 in all accredited bariatric centers of excellence in Ontario, Canada. Primary outcomes were overall postoperative complications. Secondary outcomes included early (&lt;30 days) complications, readmissions, reoperations, mortality, weight loss and comorbidities improvement at 1 and 3 year after surgery.

Results
Data of 22,981 patients &lt;65 and 532 patients ≥65 years were analyzed. Overall postoperative complications were similar between patients &lt;65 and ≥65 years (3388/22,981 [14.7%] vs. 73/532 [13.7%], p = 0.537). Early (&lt;30 days) postoperative complications, readmissions, reoperations, and mortality rates were also similar between groups. Both groups had significant weight loss and comorbidities improvement at 1- and 3-year follow-up. Patients &lt;65 years had superior weight loss (+3.5%, 95% CI: 1.6–5.4, p &lt; 0.001) and higher rates of remission for diabetes mellitus (63.8% vs. 39.3%, p &lt; 0.001), hypertension (37.9% vs. 14.5%, p &lt; 0.001), dyslipidemia (28.2% vs. 9.5%, p &lt; 0.001) and gastroesophageal reflux (65.1% vs. 24.0%, p &lt; 0.001) compared to patients ≥65 years at 3 year.

Conclusion
Patients &lt;65 and ≥65 years had similar perioperative morbidity and mortality after bariatric surgery. Even though patients &lt;65 years had overall better medium-term outcomes, bariatric surgery is safe and yields significant weight loss and comorbidities improvement in patients ≥65 years.
Long-term outcome after biliopancreatic diversion type duodenal switch: A single-center experience with up to 20 years follow-up
Authors: Süsstrunk J , Kraljević M , Schneider R , Peterli R 
Published: June 2022

Abstract

Objective
Biliopancreatic diversion type duodenal switch (BPD-DS) is the most effective bariatric procedure in terms of weight loss and remission of comorbidities but carries the risk of severe long-term side effects. The aim of this study was to analyze the long-term effects of BPD-DS on weight loss, comorbidities and reoperation rate.

Methods
This is a retrospective single-center study of prospectively collected data of all patients who underwent BPD-DS from 1999 to 2011 at a single institution.

Results
116 patients (83.6% female) underwent BPD-DS with a mean initial body mass index (BMI) of 47 ± 6.5 kg/m2. 68% of the procedures were performed in open technique and 32% laparoscopically. Common channel length was routinely 1  m, mean alimentary limb length (AL) was 1.8 ± 0.6  m and mean bilio-pancreatic limb length (BPL) was 4.9 ± 1.6  m. 76.7% of patients had laparoscopic adjustable gastric banding (LAGB) prior to BPD-DS. Mean follow-up time was 14 ± 4.4 years and follow-up rate at 5, 10 and 14 years was 95.6% (n = 108), 90% (n = 98) and 75.3% (n = 70). Mean excess BMI loss (%EBMIL) at 5, 10 and 14 years was 78% ± 24.1, 76.5% ± 26.7 and 77.8% ± 33.8, respectively. The highest %EBMIL was reached two years postoperatively with 84% ± 23.6. Complete (n = 22) or partial remission (n = 4) of type 2 diabetes mellitus was observed in 92.8% of patients. Reoperation was necessary in 33 patients (28.4%) due to malnutrition or refractory diarrhea (10), excessive weight loss (1), insufficient weight loss or weight rebound (7), reflux or stenosis (7), oxalate nephropathy (2), liver cirrhosis (1) and various/combined indications (5). Mean time to reoperation was 7.7 ± 5 years. The predominant deficiencies were vitamin D (99.1%), zinc (86.9%), iron (83.5%) and calcium (71.3%). The were no procedure-related deaths in the short- or long-term.

Conclusion
BPD-DS leads to sustainable long-term weight loss with an acceptable reoperation rate. Nevertheless, regular follow-up is necessary to detect and treat malnutrition and vitamin deficiencies.
Non-alcoholic steatohepatitis alters antigen-specific response against hepatocellular carcinoma in mice
Authors: Lacotte S , Slits F , Peloso A , Tihy M , Gex Q , Moeckli B , Toso C 
Published: June 2022

Abstract

Objective
Non-alcoholic steatohepatitis (NASH) can lead to hepatocellular carcinoma (HCC). At time immunotherapy is used as first line treatment of advanced HCC, the impact of NASH on anti-cancer immunity remains unclear. We aim at assessing the tumor-specific T cell immune response in the presence of NASH in a mouse model of HCC recurrence.

Methods
We engineered an HCC cell line (RIL-175) with a cytoplasmic expression of ovalbumin (OVA) protein. C57BL/6N mice fed a high-fat (HFD) or a control diet (CD) for 35 weeks were injected in the portal vein with 1.5.105 RIL-175-LV-OVA-GFP cells.

Results
After 35 weeks of HFD, mice were obese and developed a massive steatosis with inflammation. In the liver of HFD-fed mice, we observed an increase of the CD8+ T cell subset corresponding to an expansion of the population of CD44+ CXCR6+ PD-1+ CD8+ T cells, known to promote NASH lesions. Fourteen days after injecting RIL-LV-OVA-GFP cells, HFD-fed mice developed a higher percentage of peripheral OVA-specific CD8 T cells than CD-fed mice (8.31 vs. 3.67%; p=0.010), but these cells were not able to prevent HCC growth, resulting in larger tumors in HFD-fed mice (620 vs. 1603mm3, p=0.051). In the liver, OVA-specific CD44+ CXCR6+ CD8+ cells were present in a similar manner in CD and HFD-fed mice, however with a higher expression of PD-1 in HFD-fed mice, suggesting a lower immune activity (MFI 12605 vs. 16083, p=0.0159). Using anti-CD122 antibody acting in decreasing the CXCR6+ PD-1+ cell subset, we were able to restore OVA-specific CD8 activity through a decrease in PD-1 expression (MFI 16406 vs. 10516, p=0.0571), and to decrease HCC growth compared to HFD mice non treated with anti-CD122 (p=0.0286).

Conclusion
The immune system is altered and fails to prevent HCC growth in HFD-fed mice. This effect is primarily linked to a higher representation of CD44+ CXCR6+ PD-1+ CD8+ T cells. Treatment with anti-CD122 act on these cells, and prevent HCC growth.
CD26-inhibition correlates with the absence of chronic lung allograft dysfunction and decreases fibroblast activity in vitro
Authors: Moneke I , Ögütür E , Chatterjee S , Haberecker M , Jang J H , Fähndrich S , Senbaklavaci Ö , Faccioli E , Opitz I , Passlick B , Diederichs S , Jungraithmayr W 
Published: June 2022

Abstract

Objective
Chronic lung allograft dysfunction (CLAD) limits the survival after lung transplantation (Tx). CLAD is characterized by progressive fibrosis of small airways and lung parenchyma. No effective therapy is available that reverses or prevents CLAD. CD26 is a molecule with enzymatic activity also playing a key role in the progression of fibrotic diseases. Here, we analyzed the inhibitory effect of CD26 on fibroblast activity in vitro and the role of CD26-inhibition on allograft rejection in lung transplant patients.

Methods
Profibrogenic mRNA and protein levels were analyzed in vitro on the CD26-expressing fibroblast cell line Wi-38 using RT-qPCR and Western blot. CD26 was inhibited by Vildagliptin. Migration and proliferation activity of activated fibroblasts were analyzed by Incucyte® and Celltiter-Glo®. Characteristics of patients undergoing lung Tx between 2004 and 2021 were reviewed. Lung biopsies were analyzed by immunohistochemistry (IHC) for CD26.

Results
In vitro, the expression of profibrogenic genes (αSMA, FAPα, IGFBP7, Collagen 3 and Fibronectin) was significantly reduced in activated lung fibroblasts by Vildagliptin treatment. Also, migration and proliferation activity were attenuated by Vildagliptin. In 221 patients analyzed, CLAD was absent in 34 patients treated with the CD26-inhibitor Sitagliptin vs. an incidence of 18% in patients without Sitagliptin intake (p=0.02). Five-year survival in patients on Sitagliptin was significantly improved vs. patients without CD26-inhibitor intake (80% vs. 58%, p=0.006). Likewise, the incidence of acute cellular rejection (ACR) was significantly reduced in patients on Sitagliptin (7% vs. 35%, p=0.01). IHC of patient lung biopsies showed expression of CD26 in perifibrotic areas of CLAD lesions. Additional clinical data from University Hospital Zurich and from University Hospital Padua confirmed the finding that Sitagliptin intake correlated with the absence of acute and chronic allograft rejection.

Conclusion
CD26-inhibition attenuates key pro-fibrotic mediators and fibroblast activity in vitro. Impressively, patients on CD26-inhibitor did not show any CLAD. Moreover, ACR was significantly reduced. Gliptins which are in routine clinical use for the treatment of type II diabetes therefore seem to have great potential to be repurposed for a novel clinical application against lung allograft rejection.