bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extreme prematurity and sepsis strongly influence frequencies and functional characteristics of circulating γδ T and natural killer cells
Authors: Rahman Qazi Khaleda , Jensen Georg B , van der Heiden Marieke , Björkander Sophia , Marchini Giovanna , Jenmalm Maria C , Abrahamsson Thomas , Sverremark‐Ekström Eva 
Published: June 2021

AbstractObjectivesExtremely low gestational age neonates with extremely low birthweight (ELGAN/ELBW) are highly susceptible to infection. This is linked to their relatively immature immune system which is not yet fully compatible with an extra‐uterine environment. Here, we performed a longitudinal characterisation of unconventional T and natural killer (NK) cells in ELGAN/ELBW during their first months of life.MethodsPeripheral blood mononuclear cells were collected from 97 ELGAN/ELBW at 14 and 28 days of life and at a time point corresponding to postmenstrual week 36 + 0. γδ T‐cell, NKT‐cell, mucosa‐associated invariant T‐cell and NK cell frequencies and characteristics were analysed by flow cytometry. As control, cells from 14‐day‐old full‐term (FT) infants were included.ResultsExtreme prematurity had significant bearing on γδ T‐cell and NK cell frequencies and characteristics. ELGAN/ELBW had significantly higher proportions of γδ T cells that were skewed towards effector and effector memory phenotypes, characteristics that were maintained throughout the study period. Expression of the gut homing receptor CCR9 was also more common in γδ T cells from ELGAN/ELBW. Conversely, NK cell frequencies were markedly lower and skewed towards a cytotoxic phenotype in the ELGAN/ELBW group at 14 days of age. Culture‐proven sepsis with an onset during the first 14 days after birth further manifested these differences in the γδ T‐ and NK cell populations at 14 days of age.ConclusionPrematurity strongly influences the levels of γδ T and NK cells, in particular in cases where sepsis debuts during the first 2 weeks of life.
Leucine‐rich repeats and immunoglobulin‐like domains 1 deficiency affects hippocampal dendrite complexity and impairs cognitive function
Authors: Hita Francisco Javier , Bekinschtein Pedro , Ledda Fernanda , Paratcha Gustavo 
Published: June 2021

AbstractLeucine‐rich repeat (LRR) transmembrane proteins have been directly linked to neurodevelopmental and cognitive disorders. We have previously shown that the LRR transmembrane protein, leucine‐rich repeats and immunoglobulin‐like domains 1 (Lrig1), is a physiological regulator of dendrite complexity of hippocampal pyramidal neurons and social behavior. In this study, we performed a battery of behavioral tests to evaluate spatial memory and cognitive capabilities in Lrig1 mutant mice. The cognitive assessment demonstrated deficits in recognition and spatial memory, evaluated by novel object recognition and object location tests. Moreover, we found that Lrig1‐deficient mice present specific impairments in the processing of similar but not dissimilar locations in a spatial pattern separation task, which was correlated with an enhanced dendritic growth and branching of Doublecortin‐positive immature granule cells of the dentate gyrus. Altogether, these findings indicate that Lrig1 plays an essential role in controlling morphological and functional plasticity in the hippocampus.
Facilitation of public Payments for Ecosystem Services through local intermediaries: An institutional analysis of agri‐environmental measure implementation in Germany
Authors: Schomers Sarah , Meyer Claas , Matzdorf Bettina , Sattler Claudia 
Published: June 2021

AbstractEconomic instruments for the management of natural resources and ecosystem services governance have gained importance over the past few years. The development and implementation of large‐scale public Payments for Ecosystem Services (PES) programs as agri‐environmental measures (AEMs) depends on complex governance structures and involves diverse actors and stakeholder groups. However, research on intermediaries within PES implementation is still in its infancy. This article begins to fill this gap by providing an institutional analysis of the implications of a particular intermediary within a PES governance structure: German Landcare Associations (LCAs), which may facilitate AEM implementation in Germany. This analysis will identify the institutional challenges and constraints for cost‐effective and environmentally effective AEMs. Furthermore, we determine possible further institutional conditions that need to be addressed to better support intermediaries in AEM facilitation. To this end, the authors have determined the institutional framework conditions for the present and prospective future involvement of LCAs as intermediaries in the context of AEMs. A special focus has been placed on implications for corresponding transactions costs. The study is based on an online survey including all German LCAs and exploring LCA staff perspectives on AEM implementation. The results of this study emphasize few but severe challenging factors that adversely affect AEM implementation. We show that intermediaries can alleviate institutional implementation challenges and lower transactions costs, particularly by providing effective agri‐environmental information, training and implementational support. The positive effects on implementation are always dependent on the institutional framework and the opportunities and resources provided to the intermediaries.
The regulatory function of tandem repeat VNTR2‐1 in hTERT gene involves basic Helix–loop–helix family transcription factors
Authors: Zhu Xiaolu , Xu Tao , Zhu Jiyue 
Published: June 2021

AbstractTelomerase is a ribonucleoprotein enzyme that synthesizes telomere end sequence. The expression of hTERT gene, encoding the catalytic subunit of human telomerase, is restricted to highly proliferative tissues and is undetectable in most somatic cells. Abnormal activation of hTERT gene is found in 90% of human tumors. Previously, we identified tandem repeat of 42‐bp/unit, VNTR2‐1, in intron 2 of the hTERT gene, as a novel regulatory element important for hTERT transcription in cancer cells. In the current study, we found that multiple 42‐bp repeats of VNTR2‐1 activated luciferase gene in reporter plasmids. Mutation of the predicted cis‐regulatory elements within the 42‐bp repeats, including a E‐box motif, resulted in a partial or complete loss of its enhancer activity. Moreover, MYC family proteins, c‐MYC, MAX, and MNT, regulated hTERT gene transcription through both VNTR2‐1 and E‐boxes at the proximal hTERT promoter. Chromatin segmentation analysis of published ChIP‐sequencing data from K562 cells indicated that VNTR2‐1 was a bivalent enhancer. In telomerase‐expressing human melanoma cell line MelJuSo, deletion of VNTR2‐1 caused the hTERT promoter chromatin status to change from an active state to a repressed state, accompanied by increases of H3K27me3 and H3K9me3 marks. Therefore, we provided additional evidence for VNTR2‐1 as a functional regulatory element that regulated hTERT expression by MYC family transcription factors. These results have improved our knowledge on the functions of repetitive genomic DNAs and the regulatory mechanisms of human telomerase gene.
Improvement of biofilm formation for application in a single chamber microbial electrolysis cell
Authors: Mejía‐López Mónica , Verea Laura , Sebastian Pathiyammattom Joseph , Verde Antonio , Perez‐Sarinana Bianca Yadira , Campos José , Hernández‐Romano Jose , Moeller‐Chávez Gabriela Eleonora , Lastres Orlando , Monjardín‐Gámez José de Jesús 
Published: June 2021

AbstractAn experimental design was performed to study the combined effects of the parameters used for bacteria selective biofilm formation. The parameters were the potential applied, the time of the biofilm formation with electroactive bacteria or the biofilm formation, and the initial substrate concentration in the medium. The performance of the biofilms formed was compared by their kinetic parameter the apparent electron transfer rate constant (Kapp), which was obtained from cyclic voltammetry analysis. The results from the experimental design showed that the highest Kapp of 0.56 s−1 was with the potential applied of −0.45 V for 5 h and 12 mM of the initial substrate concentration in the medium. New values of these parameters were calculated from the statistical analysis of the experimental design results and successfully higher value of Kapp of 0.64 s−1 can be calculated and obtained. The electroactivity and capability of the biofilm for hydrogen production was also proved in a single chamber microbial electrolysis cell, and a hydrogen production yield of 0.24 m3H2/m3d was obtained. The biofilm formed with these last parameters was also identified with molecular techniques as Exiguobacterium which has barely been reported as electroactive bacteria and used for hydrogen production.
Use of artificial ground freezing in construction of cross passages under Suez Canal
Authors: Phillips Mina , Fadhel Haider , Raafat Ibrahim , El‐Kelesh Adel 
Published: June 2021

AbstractThe Artificial Ground Freezing (AGF) has demonstrated its versatility as an effective approach for both temporary ground stabilization and ground water control in almost all types of saturated soils. This paper describes the use of a closed circuit freezing system in the construction of four cross passages. The passages connect 4.8 km long twin road tunnels that have recently been constructed at depths of up to 60 m under Suez Canal in Ismailia, Egypt. The paper starts by describing the ground conditions at the locations of the cross passages and by presenting the results of laboratory tests conducted on unfrozen, frozen and thawed soil specimens. The main design criteria considered in designing the freezing works are discussed and the freezing and cross passages construction works are described. The frozen body was carefully monitored during the freezing process and construction of passages. Records of the adopted monitoring program are presented and discussed. Significant observations that contribute to effective planning of future freezing works are also presented.
Comparing prognostic utility between the 8th edition of TNM staging system and the lymph node ratio for oral squamous cell carcinoma
Authors: Beltramini Giada A. , Belloni Laura M. , Fusco Nicola , Sacconi Andrea , Muti Paola , Baj Alessandro , Bolzoni Alessandro R. , Giannì Aldo B. 
Published: June 2021

AbstractBackgroundLymph node metastasis in oral squamous cell carcinoma (OSCC) is associated with poor prognosis. The 8th edition of TNM has implemented new nodal staging criteria. We assess the prognostic utility of the lymph node ratio (LNR) and compare it to that of pN in the TNM 8th edition.MethodsOne hundred and forty‐two patients with OSCC were retrospectively studied. Nodal staging was performed using the TMN 8th edition and the prognostic value of the LNR in terms of overall survival (OS) and disease‐free survival (DFS) was evaluated.ResultsFifty‐seven patients were eligible for inclusion. The LNR was independently prognostic of OS (p = 0.02). Instead N classification was not significantly predictive of OS (p = 0.10). High LNRs resulted in decreases in OS of approximately 40% within 6 months after surgery.ConclusionsThe LNR identifies patients with poor outcomes better than N classification. The lack of reliable LNR cutoffs compromises its utility in clinical practice.
The influence of extracellular tissue on neutrophil function and its possible linkage to inflammatory diseases
Authors: Kraus Richard F. , Gruber Michael A. , Kieninger Martin 
Published: June 2021

AbstractBackground: Migration, production of reactive oxygen species (ROS), release of myeloperoxidase (MPO), and NETosis are functional immunological reactions of elementary importance for polymorphonuclear neutrophils (PMN).Unregulated inflammatory response of PMN within tissues plays a key role in the pathophysiology of several diseases. However, little is known about the behavior of PMN after migration through blood vessel walls. Therefore, we investigated the influence of the extracellular matrix (ECM) on PMN function.Materials and Methods: We established an in vitro chemotaxis model of type I and III collagen, fibrin, and herbal agarose tissues using µ‐slide chemotaxis devices and N‐formylmethionine‐leucyl‐phenylalanine (fMLP). PMN within the matrices were assessed with a fluorescent time‐lapse microscope for live‐cell imaging.Results: PMN function was obviously influenced by the ECM. Type III collagen had an inhibitory effect on PMN migration regarding track length, direction, and targeting. Type III collagen also had an accelerating effect on neutrophil ROS production. Agarose had an inhibitory effect on MPO release and fibrin a retarding effect on NETosis.Conclusion: Because of the high abundance of type III collagen in lung and skin matrices, the interaction of PMN with the respective matrix could be an important mechanism in the pathophysiology of acute respiratory distress syndrome and pyoderma gangrenosum.
To sell the cow and drink the milk: How could China harmonize its growth and risk?
Authors: Chen Ku‐Hsieh , Chen Pei‐Hua , Lin Yen‐Ju , Chi Ching‐Fang 
Published: June 2021

AbstractFacing the challenge of the new normal, mainstream public opinion advises China to adopt a conservative strategy of “slowing down the growth and lowering the leverage.” This paper proposes an alternative compatible idea of “stabilizing the growth and lowering the leverage.” For this purpose, the study first describes the investment and credit‐led mode as well as the dilemma confronted by China with an identity equation to deliberate the harmonic role played by the efficiency of aggregate social financing increments. The empirical work uses data from 31 regions in China from the first quarter of 2014 to the first quarter of 2018 as observations. The outcome shows that, if the aggregate social financing increment reaches full efficiency, the rate of output growth could provide a chance to stabilize in the short term up to around 10%, while the surging leverage and debt ratio could become moderate. There should also be an opportunity to eliminate the threat of financial risks in the medium term if combined with the deployment and implementation of ongoing supporting measures. This paper recommends a three‐step strategy of promoting efficiency, easing the risks and optimizing the structure. The expectation of “stabilizing the growth and lowering the leverage” would not be unachievable.
A novel machine learning‐based analytical framework for automatic detection of COVID‐19 using chest X‐ray images
Authors: Johri Shikhar , Goyal Mehendi , Jain Sahil , Baranwal Manoj , Kumar Vinay , Upadhyay Rahul 
Published: June 2021

AbstractConsidering the prevailing scenario of COVID‐19 pandemic, early detection of the disease is an important and crucial step in disease management. Early detection and correct treatment may limit disease progression to severe levels and prevent deaths. In addition, early isolation of infected patients will lead to control transmission rate and will possibly reduce the stress on the present healthcare system. Currently, the most common and reliable testing method available for COVID‐19 diagnosis is real‐time reverse transcription‐polymerase chain reaction (rRT‐PCR) test. However, the chest radiological (X‐ray) imaging can be used as an alternate method to rRT‐PCR test, and early COVID‐19 symptoms can be investigated by critical examination of patient's chest scans. In the present work, a novel machine learning (ML)‐based analytical framework is developed for automatic detection of COVID‐19 using chest X‐ray (CXR) images of plausible patients. The framework is designed, trained, and validated to identify four classes of CXR images namely, healthy, bacterial pneumonia, viral pneumonia, and COVID‐19. The experimental results pose the proposed framework as a potential candidate for COVID‐19 disease diagnosis using CXR images, with training, validation, and testing accuracy of 92.4%, 88.24%, and 87.13%, respectively, in four‐class classification. The comparative analysis demonstrates the better capabilities of the proposed framework COVID‐19 detection along with other types of pneumonia.
The evaluation of a multiphasic 3D‐bioplotted scaffold seeded with adipose derived stem cells to repair osteochondral defects in a porcine model
Authors: Nordberg Rachel C. , Huebner Pedro , Schuchard Karl G. , Mellor Liliana F. , Shirwaiker Rohan A. , Loboa Elizabeth G. , Spang Jeffery T. 
Published: June 2021

AbstractThere is a need for the development of effective treatments for focal articular cartilage injuries. We previously developed a multiphasic 3D‐bioplotted osteochondral scaffold design that can drive site‐specific tissue formation when seeded with adipose‐derived stem cells (ASC). The objective of this study was to evaluate this scaffold in a large animal model. Osteochondral defects were generated in the trochlear groove of Yucatan minipigs and repaired with scaffolds that either contained or lacked an electrospun tidemark and were either unseeded or seeded with ASC. Implants were monitored via computed tomography (CT) over the course of 4 months of in vivo implantation and compared to both open lesions and autologous explants. ICRS II evaluation indicated that defects with ASC‐seeded scaffolds had healing that most closely resembled the aulogous explant. Scaffold‐facilitated subchondral bone repair mimicked the structure of native bone tissue, but cartilage matrix staining was not apparent within the scaffold. The open lesions had the highest volumetric infill detected using CT analysis (p < 0.05), but the repair tissue was largely disorganized. The acellular scaffold without a tidemark had significantly more volumetric filling than either the acellular or ASC seeded groups containing a tidemark (p < 0.05), suggesting that the tidemark limited cell infiltration into the cartilage portion of the scaffold. Overall, scaffold groups repaired the defect more successfully than an open lesion but achieved limited repair in the cartilage region. With further optimization, this approach holds potential to treat focal cartilage lesions in a highly personalized manner using a human patient's own ASC cells.
Unrecognized tax benefit and its impact on firms’ financial activities: A longitudinal analysis
Authors: Ren Yi , Hsieh Chialing 
Published: June 2021

AbstractOur study investigates the unrecognized tax benefit (UTB) across firms and its impact on the firm's financial activities using the generalized estimating equations (GEEs). We find the UTB variation across firms is largely related to the firms’ operation characteristics and firms with higher UTB balances are more likely to overstate their uncertain tax positions (UTPs). Also, we find that UTB balances are positively associated with firms’ cash holding and employee stock compensation expenses. Our results provide evidence that UTB has become an important financial disclosure and have affected firms’ financial operations.
Notes from the youth mental health field: Using movement towards goals as a potential indicator of service change and quality improvement
Authors: Jacob Jenna , Edbrooke‐Childs Julian , Costa da Silva Luís , Law Duncan 
Published: June 2021

AbstractThe aim of this paper is to report our notes from the field on using movement toward goals at an aggregate level as an inference of service effectiveness. Analysis of routinely collected data from UK youth mental health services was conducted (N = 8,172, age M = 13.8, 67% female, 32% male) to explore the impact of including goal‐based outcome data in combined calculations of standardized measures based on the principles of reliable change (“measurable change”). Due to the broad nature of standardized measures, inferred validity becomes diluted in any team or service level aggregate analysis. To make inferences that are closer to the person's interpretation of their difficulties, we argue that Idiographic Patient Reported Outcome Measures (I‐PROMs) counterbalance these limitations. This is supported by our findings. The measurable change metric is the first step towards enabling national analysis of aggregated I‐PROMs. I‐PROMs, supplemented by standardized measures should be used to consider service evaluation.
Survival motor neuron deficiency slows myoblast fusion through reduced myomaker and myomixer expression
Authors: McCormack Nikki M. , Villalón Eric , Viollet Coralie , Soltis Anthony R. , Dalgard Clifton L. , Lorson Christian L. , Burnett Barrington G. 
Published: June 2021

AbstractBackgroundSpinal muscular atrophy is an inherited neurodegenerative disease caused by insufficient levels of the survival motor neuron (SMN) protein. Recently approved treatments aimed at increasing SMN protein levels have dramatically improved patient survival and have altered the disease landscape. While restoring SMN levels slows motor neuron loss, many patients continue to have smaller muscles and do not achieve normal motor milestones. While timing of treatment is important, it remains unclear why SMN restoration is insufficient to fully restore muscle size and function. We and others have shown that SMN‐deficient muscle precursor cells fail to efficiently fuse into myotubes. However, the role of SMN in myoblast fusion is not known.MethodsIn this study, we show that SMN‐deficient myoblasts readily fuse with wild‐type myoblasts, demonstrating fusion competency. Conditioned media from wild type differentiating myoblasts do not rescue the fusion deficit of SMN‐deficient cells, suggesting that compromised fusion may primarily be a result of altered membrane dynamics at the cell surface. Transcriptome profiling of skeletal muscle from SMN‐deficient mice revealed altered expression of cell surface fusion molecules. Finally, using cell and mouse models, we investigate if myoblast fusion can be rescued in SMN‐deficient myoblast and improve the muscle pathology in SMA mice.ResultsWe found reduced expression of the muscle fusion proteins myomaker (P = 0.0060) and myomixer (P = 0.0051) in the muscle of SMA mice. Suppressing SMN expression in C2C12 myoblast cells reduces expression of myomaker (35% reduction; P < 0.0001) and myomixer, also known as myomerger and minion, (30% reduction; P < 0.0001) and restoring SMN levels only partially restores myomaker and myomixer expression. Ectopic expression of myomixer improves myofibre number (55% increase; P = 0.0006) and motor function (35% decrease in righting time; P = 0.0089) in SMA model mice and enhances motor function (82% decrease in righting time; P < 0.0001) and extends survival (28% increase; P < 0.01) when administered in combination with an antisense oligonucleotide that increases SMN protein levels.ConclusionsHere, we identified reduced expression of muscle fusion proteins as a key factor in the fusion deficits of SMN‐deficient myoblasts. This discovery provides a novel target to improve SMA muscle pathology and motor function, which in combination with SMN increasing therapy could enhance clinical outcomes for SMA patients.