bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tet3 regulates cellular identity and DNA methylation in neural progenitor cells
Authors: Santiago Mafalda , Antunes Claudia , Guedes Marta , Iacovino Michelina , Kyba Michael , Reik Wolf , Sousa Nuno , Pinto Luísa , Branco Miguel R. , Marques C. Joana 
Published: October 2019

Abstract
TET enzymes oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), a process thought to be intermediary in an active DNA demethylation mechanism. Notably, 5hmC is highly abundant in the brain and in neuronal cells. Here, we interrogated the function of Tet3 in neural precursor cells (NPCs), using a stable and inducible knockdown system and an in vitro neural differentiation protocol. We show that Tet3 is upregulated during neural differentiation, whereas Tet1 is downregulated. Surprisingly, Tet3 knockdown led to a de-repression of pluripotency-associated genes such as Oct4, Nanog or Tcl1, with concomitant hypomethylation. Moreover, in Tet3 knockdown NPCs, we observed the appearance of OCT4-positive cells forming cellular aggregates, suggesting de-differentiation of the cells. Notably, Tet3 KD led to a genome-scale loss of DNA methylation and hypermethylation of a smaller number of CpGs that are located at neurogenesis-related genes and at imprinting control regions (ICRs) of Peg10, Zrsr1 and Mcts2 imprinted genes. Overall, our results suggest that TET3 is necessary to maintain silencing of pluripotency genes and consequently neural stem cell identity, possibly through regulation of DNA methylation levels in neural precursor cells.
Mild steel welding is associated with alterations in circulating levels of cancer-related proteins
Authors: Gliga Anda R. , Taj Tahir , Hedmer Maria , Assarsson Eva , Rylander Lars , Albin Maria , Broberg Karin 
Published: October 2019

Abstract
Welding fumes were recently classified as carcinogenic to humans and worldwide millions work as welders or perform welding operations. The purpose of this study was to identify new biomarkers of welding-induced carcinogenesis. We evaluated a panel of 91 putative cancer-related proteins in serum in a cohort of welders working with mild steel (n = 77) and controls (n = 94) from southern Sweden sampled on two occasions 6-year apart using a longitudinal analysis (linear mixed models). The significant results from the longitudinal analysis were tested for reproducibility in welders (n = 88) and controls (n = 69) sampled once during the same sampling period as timepoint 1 or timepoint 2 (linear regression models), i.e., in a cross-sectional setting. The models were adjusted for age, body-mass index, and use of snus. All study participants were non-smokers at recruitment. Exposure to welding fumes was assessed using questionnaires and respirable dust measurement in the breathing zone that was adjusted for personal respiratory protection equipment. The median respirable dust in welders was 0.7 (0.2–4.2) and 0.5 (0.1–1.9) mg/m3 at the first and second timepoints, respectively. We identified 14 cancer-related proteins that were differentially expressed in welders versus controls in the longitudinal analysis, out of which three were also differentially expressed in the cross-sectional analysis (cross-sectional group). Namely, syndecan 1 (SDC1), folate receptor 1 (FOLR1), and secreted protein acidic and cysteine rich (SPARC) were downregulated, in welders compared with controls. In addition, FOLR1 was negatively associated with years welding. Disease and function analysis indicated that the top proteins are related to lung cancer as well as cell invasion and migration. Our study indicates that moderate exposure to welding fumes is associated with changes in circulating levels of putative cancer-related proteins, out of which FOLR1 showed a clear dose–response relationship. It is, however, unclear to which extent these changes are adaptive or potential early biomarkers of cancer.
Chemical profiles of birch and alder bark by ambient mass spectrometry
Authors: Räsänen Riikka-Marjaana , Hieta Juha-Pekka , Immanen Juha , Nieminen Kaisa , Haavikko Raisa , Yli-Kauhaluoma Jari , Kauppila Tiina J. 
Published: October 2019

Abstract
Desorption atmospheric pressure photoionization (DAPPI) is an ambient mass spectrometry (MS) technique that allows the analysis of both polar and nonpolar compounds directly from the surfaces of various sample types. Here, DAPPI was used to study the chemical profiles in different parts of birch and alder tree barks. Four distinct fractions of Betula pendula (silver birch) bark were collected from three different developmental stages of the stem, after which the chemical profiles of the different tissue types were measured. Of special interest were triterpenoids, a class of important defensive substances, which are found in the bark of the silver birch. Additionally, the chemical profiles of lenticels and the surrounding surfaces in the phellem of B. pendula (silver birch), Alnus glutinosa (black alder), and Alnus incana (gray alder) were screened with DAPPI. Another ambient MS technique, laser ablation atmospheric pressure photoionization (LAAPPI), was further used for the mass spectrometry imaging of lenticels on the B. pendula phellem. All the studied birch bark fractions showed individual chemical profiles in DAPPI. The mass spectra from the young apical stem and the transition zone resembled each other more than the mature stem. Instead, the phellem was found to contain a high amount of triterpenoids in all the developmental stages of the stem. The most intense peaks in the DAPPI mass spectra of the birch bark fractions were those of betulin and lupeol. Betulinic and betulonic acid peaks were intense as well, and these compounds were detected especially in the lenticels of the tree samples.
The IPD Project: a centralised resource for the study of polymorphism in genes of the immune system
Authors: Maccari Giuseppe , Robinson James , Hammond John A. , Marsh Steven G. E. 
Published: October 2019

Abstract
The Immuno Polymorphism Database (IPD), https://www.ebi.ac.uk/ipd/, is a set of specialist databases that enable the study of polymorphic genes which function as part of the vertebrate immune system. The major focus is on the hyperpolymorphic major histocompatibility complex (MHC) genes and the killer-cell immunoglobulin-like receptor (KIR) genes, by providing the official repository and primary source of sequence data. Databases are centred around humans as well as animals important for food security, for companionship and as disease models. The IPD project works with specialist groups or nomenclature committees who provide and manually curate individual sections before they are submitted for online publication. To reflect the recent advance of allele sequencing technologies and the increasing demands of novel tools for the analysis of genomic variation, the IPD project is undergoing a progressive redesign and reorganisation. In this review, recent updates and future developments are discussed, with a focus on the core concepts to better future-proof the project.
A microbial expression system for high-level production of scFv HIV-neutralizing antibody fragments in Escherichia coli
Authors: Petrus Marloes L. C. , Kiefer Lukas A. , Puri Pranav , Heemskerk Evert , Seaman Michael S. , Barouch Dan H. , Arias Sagrario , van Wezel Gilles P. , Havenga Menzo 
Published: October 2019

Abstract
Monoclonal antibodies (mABs) are of great biopharmaceutical importance for the diagnosis and treatment of diseases. However, their production in mammalian expression hosts usually requires extensive production times and is expensive. Escherichia coli has become a new platform for production of functional small antibody fragment variants. In this study, we have used a rhamnose-inducible expression system that allows precise control of protein expression levels. The system was first evaluated for the cytoplasmic production of super folder green fluorescence protein (sfGFP) in various production platforms and then for the periplasmic production of the anti-HIV single-chain variable antibody fragment (scFv) of PGT135. Anti-HIV broadly neutralizing antibodies, like PGT135, have potential for clinical use to prevent HIV transmission, to promote immune responses and to eradicate infected cells. Different concentrations of L-rhamnose resulted in the controlled production of both sfGFP and scFv PGT135 antibody. In addition, by optimizing the culture conditions, the amount of scFv PGT135 antibody that was expressed soluble or as inclusions bodies could be modulated. The proteins were produced in batch bioreactors, with yields of 4.9 g/L for sfGFP and 0.8 g/L for scFv. The functionality of the purified antibodies was demonstrated by their ability to neutralize a panel of different HIV variants in vitro. We expect that this expression system will prove very useful for the development of a more cost-effective production process for proteins and antibody fragments in microbial cells.
Evolutionary dynamics of competing phenotype-structured populations in periodically fluctuating environments
Authors: Ardaševa Aleksandra , Gatenby Robert A. , Anderson Alexander R. A. , Byrne Helen M. , Maini Philip K. , Lorenzi Tommaso 
Published: October 2019

Abstract
Living species, ranging from bacteria to animals, exist in environmental conditions that exhibit spatial and temporal heterogeneity which requires them to adapt. Risk-spreading through spontaneous phenotypic variations is a known concept in ecology, which is used to explain how species may survive when faced with the evolutionary risks associated with temporally varying environments. In order to support a deeper understanding of the adaptive role of spontaneous phenotypic variations in fluctuating environments, we consider a system of non-local partial differential equations modelling the evolutionary dynamics of two competing phenotype-structured populations in the presence of periodically oscillating nutrient levels. The two populations undergo heritable, spontaneous phenotypic variations at different rates. The phenotypic state of each individual is represented by a continuous variable, and the phenotypic landscape of the populations evolves in time due to variations in the nutrient level. Exploiting the analytical tractability of our model, we study the long-time behaviour of the solutions to obtain a detailed mathematical depiction of the evolutionary dynamics. The results suggest that when nutrient levels undergo small and slow oscillations, it is evolutionarily more convenient to rarely undergo spontaneous phenotypic variations. Conversely, under relatively large and fast periodic oscillations in the nutrient levels, which bring about alternating cycles of starvation and nutrient abundance, higher rates of spontaneous phenotypic variations confer a competitive advantage. We discuss the implications of our results in the context of cancer metabolism.
Poly-glycine–alanine exacerbates C9orf72 repeat expansion-mediated DNA damage via sequestration of phosphorylated ATM and loss of nuclear hnRNPA3
Authors:   German Consortium for Frontotemporal Lobar Degeneration, Nihei Yoshihiro ,   Bavarian Brain Banking Alliance, Mori Kohji , Werner Georg , Arzberger Thomas , Zhou Qihui , Khosravi Barham , Japtok Julia , Hermann Andreas , Sommacal Andreas , Weber Markus , Kamp Frits , Nuscher Brigitte , Edbauer Dieter , Haass Christian 
Published: October 2019

Abstract
Repeat expansion in C9orf72 causes amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Expanded sense and antisense repeat RNA transcripts in C9orf72 are translated into five dipeptide-repeat proteins (DPRs) in an AUG-independent manner. We previously identified the heterogeneous ribonucleoprotein (hnRNP) A3 as an interactor of the sense repeat RNA that reduces its translation into DPRs. Furthermore, we found that hnRNPA3 is depleted from the nucleus and partially mislocalized to cytoplasmic poly-GA inclusions in C9orf72 patients, suggesting that poly-GA sequesters hnRNPA3 within the cytoplasm. We now demonstrate that hnRNPA3 also binds to the antisense repeat RNA. Both DPR production and deposition from sense and antisense RNA repeats are increased upon hnRNPA3 reduction. All DPRs induced DNA double strand breaks (DSB), which was further enhanced upon reduction of hnRNPA3. Poly-glycine–arginine and poly-proline-arginine increased foci formed by phosphorylated Ataxia Telangiectasia Mutated (pATM), a major sensor of DSBs, whereas poly-glycine–alanine (poly-GA) evoked a reduction of pATM foci. In dentate gyri of C9orf72 patients, lower nuclear hnRNPA3 levels were associated with increased DNA damage. Moreover, enhanced poly-GA deposition correlated with reduced pATM foci. Since cytoplasmic pATM deposits partially colocalized with poly-GA deposits, these results suggest that poly-GA, the most frequent DPR observed in C9orf72 patients, differentially causes DNA damage and that poly-GA selectively sequesters pATM in the cytoplasm inhibiting its recruitment to sites of DNA damage. Thus, mislocalization of nuclear hnRNPA3 caused by poly-GA leads to increased poly-GA production, which partially depletes pATM, and consequently enhances DSB.
Simultaneous multi-descent regression and feature learning for facial landmarking in depth images
Authors: Križaj Janez , Peer Peter , Štruc Vitomir , Dobrišek Simon 
Published: October 2019

AbstractFace alignment (or facial landmarking) is an important task in many face-related applications, ranging from registration, tracking, and animation to higher-level classification problems such as face, expression, or attribute recognition. While several solutions have been presented in the literature for this task so far, reliably locating salient facial features across a wide range of posses still remains challenging. To address this issue, we propose in this paper a novel method for automatic facial landmark localization in 3D face data designed specifically to address appearance variability caused by significant pose variations. Our method builds on recent cascaded regression-based methods to facial landmarking and uses a gating mechanism to incorporate multiple linear cascaded regression models each trained for a limited range of poses into a single powerful landmarking model capable of processing arbitrary-posed input data. We develop two distinct approaches around the proposed gating mechanism: (1) the first uses a gated multiple ridge descent mechanism in conjunction with established (hand-crafted) histogram of gradients features for face alignment and achieves state-of-the-art landmarking performance across a wide range of facial poses and (2) the second simultaneously learns multiple-descent directions as well as binary features that are optimal for the alignment tasks and in addition to competitive landmarking results also ensures extremely rapid processing. We evaluate both approaches in rigorous experiments on several popular datasets of 3D face images, i.e., the FRGCv2 and Bosphorus 3D face datasets and image collections F and G from the University of Notre Dame. The results of our evaluation show that both approaches compare favorably to the state-of-the-art, while exhibiting considerable robustness to pose variations.
Cervical radiculopathy: is a prosthesis preferred over fusion surgery? A systematic review
Authors: Goedmakers Caroline M. W. , Janssen Tessa , Yang Xiaoyu , Arts Mark P. , Bartels Ronald H. M. A. , Vleggeert-Lankamp Carmen L. A. 
Published: October 2019

Abstract

Background
Meta-analyses on the comparison between fusion and prosthesis in the treatment of cervical radiculopathy mainly analyse studies including mixed patient populations: patients with radiculopathy with and without myelopathy. The outcome for patients with myelopathy is different compared to those without. Furthermore, apart from decompression of the spinal cord, restriction of motion is one of the cornerstones of the surgical treatment of spondylotic myelopathy. From this point of view, the results for arthroplasty might be suboptimal for this category of patients. Comparing clinical outcome in patients exclusively suffering from radiculopathy is therefore a more valid method to compare the true clinical effect of the prosthesis to that of fusion surgery.

Aim
The objective of this study was to compare clinical outcome of cervical arthroplasty (ACDA) to the clinical outcome of fusion (ACDF) after anterior cervical discectomy in patients exclusively suffering from radiculopathy, and to evaluate differences with mixed patient populations.

Methods
A literature search was completed in PubMed, EMBASE, Web of Science, COCHRANE, CENTRAL and CINAHL using a sensitive search strategy. Studies were selected by predefined selection criteria (i.a.) patients exclusively suffering from cervical radiculopathy), and risk of bias was assessed using a validated Cochrane Checklist adjusted for this purpose. An additional overview of results was added from articles considering a mix of patients suffering from myelopathy with or without radiculopathy.

Results
Eight studies were included that exclusively compared intervertebral devices in radiculopathy patients. Additionally, 29 articles concerning patients with myelopathy with or without radiculopathy were studied in a separate results table. All articles showed intermediate to high risk of bias. There was neither a difference in decrease in mean NDI score between the prosthesis (20.6 points) and the fusion (20.3 points) group, nor was there a clinically important difference in neck pain (VAS). Comparing these data to the mixed population data demonstrated comparable mean values, except for the 2-year follow-up NDI values in the prosthesis group: mixed group patients that received a prosthesis reported a mean NDI score of 15.6, indicating better clinical outcome than the radiculopathy patients that received a prosthesis though not reaching clinical importance.

Conclusions
ACDF and ACDA are comparably effective in treating cervical radiculopathy due to a herniated disc in radiculopathy patients. Comparing the 8 radiculopathy with the 29 mixed population studies demonstrated that no clinically relevant differences were present in clinical outcome between the two types of patients.

Graphic abstract
These slides can be retrieved under Electronic Supplementary Material.
Is there a role for prophylactic mesh in abdominal wall closure after emergency laparotomy? A systematic review and meta-analysis
Authors: Burns F. A. , Heywood E. G. , Challand C. P. , Lee Matthew J. 
Published: October 2019

Abstract

Background
Incisional hernias are a common complication of emergency laparotomy and are associated with significant morbidity. Recent studies have found a reduction in incisional hernias when mesh is placed prophylactically during abdominal closure in elective laparotomies. This systematic review will assess the safety and efficacy of prophylactic mesh placement in emergency laparotomy.

Methods
A systematic review was performed according to the PROSPERO registered protocol (CRD42018109283). Papers were dual screened for eligibility, and included when a comparison was made between closure with prophylactic mesh and closure with a standard technique, reported using a comparative design (i.e. case–control, cohort or randomised trial), where the primary outcome was incisional hernia. Bias was assessed using the Cochrane risk of bias in non-randomised studies tool. A meta-analysis of incisional hernia rate was performed to estimate risk ratio using a random effects model (Mantel–Haenszel approach).

Results
332 studies were screened for eligibility, 29 full texts were reviewed and 2 non-randomised studies were included. Both studies were biased due to confounding factors, as closure technique was based on patient risk factors for incisional hernia. Both studies found significantly fewer incisional hernias in the mesh groups [3.2% vs 28.6% (p < 0.001) and 5.9% vs 33.3% (p = 0.0001)]. A meta-analysis of incisional hernia risk favoured prophylactic mesh closure [risk ratio 0.15 (95% CI 0.6–0.35, p < 0.001)]. Neither study found an association between mesh and infection or enterocutaneous fistula.

Conclusion
This review found that there are limited data to assess the effect or safety profile of prophylactic mesh in the emergency laparotomy setting. The current data cannot reliably assess the use of mesh due to confounding factors, and a randomised controlled trial is required to address this important clinical question.
Empirical mode decomposition of multiphase flows in porous media: characteristic scales and speed of convergence
Authors: Echebarrena Nicolás , Mininni Pablo D. , Moreno Gustavo A. 
Published: October 2019

Abstract
We apply a proper orthogonal decomposition (POD) to data stemming from numerical simulations of a fingering instability in a multiphase flow passing through obstacles in a porous medium, to study water injection processes in the production of hydrocarbon reservoirs. We show that the time evolution of a properly defined flow correlation length can be used to identify the onset of the fingering instability. Computation of characteristic lengths for each of the modes resulting from the POD provides further information on the dynamics of the system. Finally, using numerical simulations with different viscosity ratios, we show that the convergence of the POD depends non-trivially on whether the fingering instability develops or not. This result has implications on proposed methods to decrease the dimensionality of the problem by deriving reduced dynamical systems after truncating the system’s governing equations to a few POD modes.
Selection of Sustainable Food Waste Valorisation Routes: A Case Study with Barley Field Residue
Authors: Stone Jamie , Garcia-Garcia Guillermo , Rahimifard Shahin 
Published: October 2019

Abstract

Purpose
It is increasingly accepted in the food and drink manufacturing sector that there is a need to manage unavoidable food waste more sustainably. Yet to do so requires careful balancing of environmental, social and economic performance of any given treatment method alongside its technological maturity and alignment with that company’s wider business goals. The purpose of this article is to apply a novel Sustainable Waste Valorisation Identification (SWaVI) framework which considers these criteria to a case study with Molson Coors to identify whether the current strategy of using In Field Barley Straw Residue as animal feed is the most sustainable.

Methods
Data was collected via a series of interviews with Molson Coors in spring 2017. Data analysis used a hybrid approach combining Cost–Benefit Analysis and Life-Cycle Assessment with a weighted summation variant of Multi-Criteria Decision Analysis to facilitate comparison of supercritical CO2 extraction of wax from straw, with the current strategy of selling that straw as animal feed.

Results
Application of the SWaVI framework suggests that supercritical CO2 extraction of wax from straw offers a slightly worse Net Present Value compared to sale as animal feed (£89.1 million compared to £95.3 million) but superior social impacts, technological maturity and alignment with company goals making it superior overall.

Conclusions
Whilst the supercritical CO2 extraction of wax offers the best sustainability and business case performance for Molson Coors, a range of other factors such as long-term market demand, alignment with relevant legislation, and displacement effects on supply chain stakeholders must be considered.

Graphic Abstract