bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of 2019 novel coronavirus in semen and testicular biopsy specimen of COVID-19 patients
Authors: Song Ci , Wang Yan , Li Weiqin , Hu Bicheng , Chen Guohua , Xia Ping , Wang Wei , Li Chaojun , Hu Zhibin , Yang Xiaoyu , Yao Bing , Liu Yun
Published: April 2020

Background

As of March 11, 2020, the COVID-19 outbreak was declared as a pandemic. Expending our understanding of the transmission routes of the viral infection is crucial in controlling the outbreak. It is unclear whether the 2019 novel coronavirus (2019-nCoV) can directly infect the testes or male genital tract and be sexually transmitted from males.

Methods

From January 31 to March 14, 2020, 12 patients in recovery and one patient died of COVID-19 were included in this descriptive study. The clinical characteristics, laboratory findings, chest CT scans and outcome data were recorded. To examine whether there is sexual transmission from male, we employed realtime polymerase chain reaction testing (RT-PCR) to detect 2019-nCov in semen or testicular biopsy specimen.

Findings

The age range of the 12 patients in recovery was 22-38 years. None of the patients developed severe COVID-19 pneumonia. As of March 14, 2020, ten patients discharged from the hospital while the rest 2 had developed into recovery stage. All of the 12 patients in recovery tested negative for 2019-nCoV RNA in semen samples. Another patient aged 67 died in March 10, 2020, whose tissue sample via testicular biopsy was also tested negative for viral RNA.

Conclusion

No positive RT-PCR result was found in the semen or testicular biopsy specimen. The results from this study show no evidence of sexual transmission of 2019-nCov from males.
Nucleosome assembly and disassembly pathways
Authors: Hatakeyama A. , Retureau R. , Pasi M. , Hartmann B. , Nogues C. , Buckle M.
Published: April 2020

Nucleosome assembly and disassembly play a central role in the regulation of gene expression. Here we use PhAST (Photochemical Analysis of Structural Transitions) to monitor at the base pair level, structural alterations induced all along DNA upon histone binding or release. By offering the first consistent, detailed comparison of nucleosome assembly and disassemblyin vitro, we are able to reveal similarities and differences between the two processes. We identify multiple intermediate states characterised by specific PhAST signatures; revealing a complexity that goes beyond the known sequential events involving (H3-H4)2tetramer and H2A-H2B heterodimers. Such signatures localise and quantify the extent of the asymmetry of DNA/histone interactions with respect to the nucleosome dyad. This asymmetry is therefore defined by the localisation and amplitude of the signals. The localisation of the signal is consistent between assembly and disassembly and dictated by the DNA sequence. However, the amplitude component of this asymmetry not only evolves during the assembly and disassembly but does so differently between the two processes.

Understanding the regulation of gene expression requires a complete knowledge of nucleosome dynamics. Our unexpected observation of differences between assembly and disassembly opens up new avenues to define the role of the DNA sequence in these processes. Overall, we provide new insights into how the intrinsic properties of DNA are integrated into a holistic mechanism that controls chromatin structure.

Statement of Significance

This manuscript addresses the question of nucleosome dissociation compares with association. We used PhAST which is a non-intrusive photochemical technique to follow nucleosome dynamics at base pair resolution. We observed structural asymmetry during nucleosome turnover. We also showed for the first time that the process of nucleosome dissociation is not a reversal of association. This asymmetry favours intermediate states involved in chromatin organisation suggesting novel models for the role of nucleosome turnover in the epigenetic regulation of gene expression.
Gene deletion studies reveal a critical role for prostamide/prostaglandin F2αsynthase in prostamide F2αformation
Authors: Bertrand Jacques A , Woodward David F , Sherwood Joseph M , Spenlehauer Alice , Silvestri Cristoforo , Piscitelli Fabiana , Di Marzo Vincenzo , Yamazaki Maya , Sakimura Kenji , Watanabe Kikuko , Overby Darryl R
Published: April 2020

Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide and prostaglandin F2α.The importance of this enzyme, relative to the aldoketoreductase (AKR) series, in providing functional tissue prostamide F2αlevels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (fam213b) was accomplished by a two exon disruption. Prostamide F2αlevels in WT and PM/PGFS KO mice were determined by LC/MS/MS. Intraocular pressure was measured by tonometry and outflow facility was measured by theiPerfusionmethod in enucleated mouse eyes. Deletion of fam213b had no observed effect on behavior, appetite, or fertility. Intraocular pressure was significantly elevated by approximately 4 mmHg in PM/PGFS KO mice compared to littermate WT mice. No effect on pressure dependent outflow facility occurred, which is consistent with the typically reported prostanoid effect of increasing outflow through the unconventional pathway. The elevation of intraocular pressure caused by deletion of the gene encoding the PM/PGFS enzyme likely results from a diversion of the endoperoxide precursor pathway to provide increased levels of those prostanoids that raise intraocular pressure, namely prostaglandin D2(PGD2), thromboxane A2(TxA2). It follows that PM/PGFS may serve an important regulatory role in the eye by providing PGF2αand prostamide F2αto constrain the influence of those prostanoids that raise intraocular pressure.
Hypoxia-related radiomics predict immunotherapy response: A multi-cohort study of NSCLC
Authors: Tunali Ilke , Tan Yan , Gray Jhanelle E. , Katsoulakis Evangelia , Eschrich Steven A. , Saller James , Boyle Theresa , Qi Jin , Guvenis Albert , Gillies Robert J. , Schabath Matthew B.
Published: April 2020

Checkpoint blockade immunotherapy provides improved long-term survival in a subset of advanced stage non-small cell lung cancer (NSCLC) patients. However, highly predictive biomarkers of immunotherapy response are unmet clinical need. In this study, we utilized pre-treatment clinical factors and quantitative image-based biomarkers (radiomics) to identify a parsimonious model that predicts survival outcomes among NSCLC patients treated with immunotherapy. The NSCLC patients treated with single or double agent immunotherapy were included in three different cohorts: Training (N = 180), test (N = 90) and validation (N = 62) cohorts. The models were created based on overall survival (OS) and were additionally assessed for progression-free survival (PFS). Including most predictive radiomic features and clinical covariates, Classification and Regression Tree analysis was applied to stratify patients into survival risk-groups in the training cohort. The risk groups were later generated in the test and validation cohorts. Four independent NSCLC cohorts (total N = 446) were utilized for further validation of the radiomic signature. The biological underpinnings of the most informative radiomics were assessed using gene expression data from a radiogenomics dataset and validated by immunohistochemistry data (IHC). A parsimonious clinical-radiomics model was found to be significantly associated with OS and PFS after stratifying patients into groups of low-, moderate-, high-, and very-high risk of death and progression. This trained model was further tested and validated in two independent cohorts. When the extreme phenotypes were compared, the very-high risk group was found to be associated with extremely poor OS in both the test (hazard ratio [HR] = 5.35, 95% confidence interval [CI]: 2.14 – 13.36; 1-year OS = 11.1%) and validation (HR = 13.81, 95% CI: 2.58 – 73.93; 1-year OS = %47.6) cohorts when compared to the low risk group (HRs = 1.00; 1-year OS = 85.0% & 80.2%). Similar findings were observed for PFS. The final radiomic feature (GLCM inverse difference) was associated with OS in four independent NSCLC cohorts and was found to be positively associated with the hypoxia-related carbonic anhydrase, CAIX, by gene expression profiling and immunohistochemistry. We validated a novel clinical-radiomics model that is associated with OS and PFS among NSCLC patients treated with immunotherapy and identified a highly vulnerable subset of patients that are unlikely to respond to immunotherapy. The most informative radiomic feature was associated with CAIX, a marker of tumor hypoxia, tumor acidosis, and treatment resistance.
Pod indehiscence in common bean is associated to the fine regulation ofPvMYB26and a non-functional abscission layer
Authors: Di Vittori Valerio , Bitocchi Elena , Rodriguez Monica , Alseekh Saleh , Bellucci Elisa , Nanni Laura , Gioia Tania , Marzario Stefania , Logozzo Giuseppina , Rossato Marzia , De Quattro Concetta , Murgia Maria L. , José Ferreira Juan , Campa Ana , Xu Chunming , Fiorani Fabio , Sampathkumar Arun , Fröhlich Anja , Attene Giovanna , Delledonne Massimo , Usadel Björn , Fernie Alisdair R. , Rau Domenico , Papa Roberto
Published: April 2020

In legumes, pod shattering occurs when mature pods dehisce along the sutures, and detachment of the valves promotes seed dispersal. InPhaseolus vulgaris, the major locusqPD5.1-Pvfor pod indehiscence was identified recently. We developed a BC4/F4 introgression line population and narrowed the major locus down to a 22.5-kb region. Here, gene expression and a parallel histological analysis of dehiscent and indehiscent pods identified anAtMYB26orthologue as the best candidate for loss of pod shattering, on a genomic region ~11 kb downstream of the highest associated peak. Based on mapping and expression data, we propose early and fine up-regulation ofPvMYB26in dehiscent pods. Detailed histological analysis establishes that pod indehiscence is associated to the lack of a functional abscission layer in the ventral sheath, and that the key anatomical modifications associated with pod shattering in common bean occur early during pod development. We finally propose that loss of pod shattering in legumes resulted from histological convergent evolution and that this is the result of selection at orthologous loci.

One-sentence summary

A non-functional abscission layer determines the loss of pod shattering; mapping data, and parallel gene expression and histological analysis supportPvMYB26as the candidate gene for pod indehiscence.
Computed Tomography Findings and Short-term follow-up with Novel Coronavirus Pneumonia
Authors: Qi Shi , Guo Hui , Shao Hua , Lan Siqin , He Yuanlin , Tiheiran Maijudan , Li Hongjun
Published: April 2020

Objective

To assess the characteristics of computed tomography (CT) features and changes in CT monitoring in patients with novel coronavirus pneumonia (NCP).

Methods

In this retrospective, two-center study, we reviewed the medical records of 57 patients with NCP in CT from January 21 to February 12, 2020. Cases were confirmed by the results of nucleic acid test positive, and were analyzed for demographic, clinical, and CT features.

Results

Of the 57 patients, 31cases were male, and 45.6% were female. The average age was 46.5 ± 15.8 years. Patients had fever (84.2%), cough (49.1%), weak (31.6%), muscle ache (17.5%), shortness of breath (12.3%). The distribution of abnormality was a subpleural lesions in 51 cases, with 96.5% ground-glass opacity (GGO) and 68.4% consolidation. Another observation reveals 45.6% fibrosis, 33.3% lymph node enlargement, 21.1% pleural thickening, 17.5% small nodule, 7.0% white lung, 5.3% emphysema, and 3.5% bronchiectasis. Importantly, the group of men had more septal thickening and air trapping than the female group (p<0.05); Compared with the younger, the elderly had higher of subpleural lesion, interlobular septal thickening and pleural thickening (p<0.05). In the first monitoring, there were 37.3% improvement, 60.8% progress. In the second monitoring, there were 55% improvement, 35% progress. The improvement rate during the third follow-up visit was 100%.

Conclusions

CT features and CT dynamic observation play a vital role in the diagnosis and treatment with NCP. It is conducive to early diagnosis, deepen the knowledge of NCP and accumulate experience.

Key points

Bilateral and subpleural regions on CT are common in patients with novel coronavirus pneumonia (NCP), which were more extensive GGOs than consolidation.

At CT, NCP shows GGOs without or with consolidation, which most of the patients appear interlobular interstitium thickening, vascular bundle thickening, air bronchogram, and fibrosis. In patients with fever in close contact with eruption areas of 2019-nCoV, familiarity with the CT findings may help with early diagnosis, early isolation, and management.
Live-cell 3D single-molecule tracking reveals how NuRD modulates enhancer dynamics
Authors: Basu S , Shukron O , Hall D , Parutto P , Ponjavic A , Shah D , Boucher W , Lando D , Zhang W , Reynolds N , Sober LH , Jartseva A , Ragheb R , Ma X , Cramard J , Floyd R , Brown G , Balmer J , Drury TA , Carr AR , Needham L-M , Aubert A , Communie G , Gor K , Steindel M , Morey L , Blanco E , Bartke T , Di Croce L , Berger I , Schaffitzel C , Lee SF , Stevens TJ , Klenerman D , Hendrich BD , Holcman D , Laue ED
Published: April 2020

Enhancer-promoter dynamics are crucial for the spatiotemporal control of gene expression, but it remains unclear whether these dynamics are controlled by chromatin regulators, such as the nucleosome remodelling and deacetylase (NuRD) complex. The NuRD complex binds to all active enhancers to modulate transcription and here we use Hi-C experiments to show that it blurs TAD boundaries and increases the proximity of intermediate-range (~1 Mb) genomic sequences and enhancer-promoter interactions. To understand whether NuRD alters the dynamics of 3D genome structure, we developed an approach to segment and extract key biophysical parameters from 3D single-molecule trajectories of the NuRD complex determined using live-cell imaging. Unexpectedly, this revealed that the intact NuRD complex decompacts chromatin structure and makes NuRD-bound enhancers move faster, increasing the overall volume of the nucleus that these key regulatory regions explore. Interestingly, we also uncovered a rare fast-diffusing state of NuRD bound enhancers that exhibits directed motion. The NuRD complex reduces the amount of time that enhancers remain in this fast-diffusing state, which we propose might otherwise re-organise enhancer-promoter proximity. Thus, we uncover an intimate connection between a chromatin remodeller and the spatial dynamics of the local regions of the genome to which it binds.
DENSITIES, PLANT SIZES, AND SPATIAL DISTRIBUTIONS OF SIX WILD POPULATIONS OFLOPHOPHORA WILLIAMSII(CACTACEAE) IN TEXAS, U.S.A
Authors: Ermakova Anna , Whiting Carolyn V. , Trout Keeper , Clubbe Colin , Terry Martin K. , Fowler Norma
Published: April 2020

Lophophora williamsii(Cactaceae) is thought to be threatened by habitat loss and overharvesting. However, basic demographic and habitat information to evaluate its conservation status has been lacking. We surveyed six wild populations of this species, three in South Texas and three in West Texas, to begin to address this gap. We found high levels of heterogeneity in plant presence and density at multiple spatial scales. While plant densities were not consistently different between South and West Texas, plants were significantly larger in West Texas. The two regions differ strongly in precipitation, temperature, elevation, and topography, all of which are correlated at the regional scale. Therefore, it was not possible to identify which of these variables, or other factors such as competition and human harvesting, may be responsible for the regional differences in plant size. However, our results provide initial information for determining the conservation status of this species.

Lophophora williamsii (Cactaceae)se considera amenazada por la pérdida de hábitat y cosecha excesiva. Sin embargo, se carece de información demográfica y ambiental básica para evaluar su estado de conservación. Para abordar este déficit, examinamos seis poblaciones salvajes de esta especie (tres en el sur y tres en el oeste de Texas respectivamente). Encontramos altos niveles de heterogeneidad en la presencia y densidad de plantas en múltiples escalas espaciales. Las densidades no son consistentemente diferentes entre el sur y el oeste, pero las plantas son significativamente más grandes en el oeste. Las dos regiones difieren notablemente en precipitación, temperatura, elevación y topografía. Todas estas variables están correlacionadas a escala regional, por lo que no es posible identificar cuál de ellas (u otros factores como la competencia y la cosecha humana) causan las diferencias regionales observadas en el tamaño de la planta. Nuestros resultados proporcionan información fundamental para determinar el estado de conservación de esta especie.
Mediator complex subunit Med19 binds directly GATA DNA-binding zinc finger and functions with Med1 in GATA-driven gene regulationin vivo
Authors: Immarigeon Clément , Bernat-Fabre Sandra , Guillou Emmanuelle , Verger Alexis , Prince Elodie , Benmedjahed Mohamed A. , Payet Adeline , Couralet Marie , Monte Didier , Villeret Vincent , Bourbon Henri-Marc , Boube Muriel
Published: April 2020

The evolutionarily-conserved multiprotein Mediator complex (MED) serves as an interface between DNA-bound transcription factors (TFs) and the RNA Polymerase II machinery. It has been proposed that each TF interacts with a dedicated MED subunit to induce specific transcriptional responses. However, binary MED subunit - TF partnerships are probably oversimplified models. UsingDrosophilaTFs of the GATA family - Pannier (Pnr) and Serpent (Srp) - as a model, we have previously established GATA cofactor evolutionarily-conserved function for the Med1 Mediator subunit. Here, we show that another subunit, Med19, is required for GATA-dependent gene expression and interacts physically with Pnr and Srpin cellulo, in vivoandin vitrothrough their conserved C-zinc finger (ZF), indicating general GATA co-activator functions. Interestingly, Med19 is critical for the regulation of all tested GATA target genes which is not the case for Med1, suggesting differential use of MED subunits by GATAs depending on the target gene. Lastly, despite their presumed distant position within the MED middle module, both subunits interact physically. In conclusion, our data shed new light first on the MED complex, engaging several subunits to mediate TF-driven transcriptional responses and second, on GATA TFs, showing that ZF DNA-binding domain also serves for transactivation.
POMK regulates dystroglycan function via LARGE-mediated elongation of matriglycan
Authors: Walimbe Ameya S. , Okuma Hidehiko , Joseph Soumya , Yang Tiandi , Yonekawa Takahiro , Hord Jeffrey M. , Venzke David , Anderson Mary E. , Torelli Silvia , Manzur Adnan , Devereaux Megan , Cuellar Marco , Prouty Sally , Landa Saul Ocampo , Yu Liping , Xiao Junyu , Dixon Jack E. , Muntoni Francesco , Campbell Kevin P.
Published: April 2020

Matriglycan [-GlcA-β1,3-Xyl-α1,3-]nserves as a scaffold in many tissues for extracellular matrix proteins containing laminin-G domains including laminin, agrin, and perlecan. Like-acetylglucosaminyltransferase-1 (LARGE) synthesizes and extends matriglycan on α-dystroglycan (α-DG) during skeletal muscle differentiation and regeneration; however, the mechanisms which regulate matriglycan elongation are unknown. Here, we show thatProtein O-Mannose Kinase (POMK), which phosphorylates mannose of core M3 (GalNac-β1,3-GlcNac-β1,4-Man) preceding matriglycan synthesis, is required for LARGE-mediated generation of full-length matriglycan on α-DG (∼150 kDa). In the absence ofPOMK, LARGE synthesizes a very short matriglycan resulting in a ∼90 kDa α-DG in mouse skeletal muscle which binds laminin but cannot prevent eccentric contraction-induced force loss or muscle pathology. Solution NMR spectroscopy studies demonstrate that LARGE directly interacts with core M3 and binds preferentially to the phosphorylated form. Collectively, our study demonstrates that phosphorylation of core M3 byPOMKenables LARGE to elongate matriglycan on α-DG, thereby preventing muscular dystrophy.
Defining an age cut-off for older offenders: a systematic review of literature
Authors: Merkt Helene , Haesen Sophie , Meyer Leila , Kressig Reto W. , Elger Bernice S. , Wangmo Tenzin
Published: April 2020

Purpose

In the literature, 65 years is commonly used as the age to designate an older person in the community. When studying older prisoners, there is much variation. The purpose of this paper is to investigate how researchers define older offenders and for what reasons.

Design/methodology/approach

The authors reviewed articles on health and well-being of older offenders to assess terminology used to describe this age group, the chosen age cut-offs distinguishing younger offenders from older offenders, the arguments provided to support this choice as well as the empirical base cited in this context.

Findings

The findings show that the age cut-off of 50 years and the term “older” were most frequently used by researchers in the field. The authors find eight main arguments given to underscore the use of specific age cut-offs delineating older offenders. They outline the reasoning provided for each argument and evaluate it for its use to define older offenders.

Originality/value

With this review, it is hoped to stimulate the much-needed discussion advancing towards a uniform definition of the older offender. Such a uniform definition would make future research more comparable and ensure that there is no ambiguity when researchers state that the study population is “older offenders”.
Learning environment, students' attitude and intention to enhance current knowledge in the context of choosing accounting career
Authors: Hatane Saarce Elsye , Setiono Felicia Jesslyn , Setiawan Fannie Felita , Semuel Hatane , Mangoting Yenni
Published: April 2020

Purpose

This research examines the influence of the learning environment and students' attitudes towards choosing an accounting career mediated by intention to enhance the current knowledge.

Design/methodology/approach

The online survey is adopted to test the research model of this research. There are 503 useable responses collected with the effective response rate of 72 per cent. Data analysis and hypothesis testing use Partial Least Square as part of the Structural Equation Modelling technique.

Findings

The results of this research indicate that accounting students possess positive attitude both towards the intention to enhance the current knowledge and choosing their accounting career. The learning environment includes educators and friends who give significant influence on students' intention. Besides, current knowledge enhancement is also discovered to be able to mediate the link between attitude, learning environment and intention to choose accounting career.

Research limitations/implications

Different generations may generate either different perception or different orientation in choosing accounting career. Therefore, future research can consider wider coverage and more updated object.

Practical implications

Findings of this research suggest that periodic improvement and renewal are necessary to administer to create an optimum learning environment, in term of teachers' capacity, teaching materials and supporting social environment.

Originality/value

This research contributes to any research related to attitudes towards choosing an accounting career. This study is the leading study that combines students' attitudes, learning environment, current knowledge enhancement, and career choice in one single model.
Does emotional labor color service actions in customer buying?
Authors: Seger-Guttmann Tali , Medler-Liraz Hana
Published: April 2020

Purpose

Service research has highlighted the role of emotional labor in service delivery but has neglected service employees’ actions. This study aims to distinguish between the recurrent in-role and extra-role actions of service employees and to examine the joint effect of service employees’ actions and their emotional labor, which may color these actions on customer buying behavior (number of purchased items and total bill).

Design/methodology/approach

Phase I comprised two studies: Study 1 examined 70 service interaction videos to identify employees’ service actions, and Study 2 quantitatively validated the most frequent employee actions, used for further study, by examining 40 employee–customer interactions in fashion stores. For Phase II, Study 3 derived data from 60 service employees’ diaries to predict the joint effect of performed emotional labor and service actions on customer buying behavior.

Findings

Findings revealed that emotional labor moderated the relationship between service actions and customer buying behavior. The relationship between in-role/extra-role actions and buying behavior was stronger in the lower surface-acting (less emotional faking) condition, whereas the relationship between in-role/extra-role actions and buying behavior was stronger for the higher deep-acting (more emotionally authentic) condition.

Practical implications

Service organizations should not limit training to the more easily attained service actions. This possibility may be lacking if it ignores the emotional component that accompanied the action. This may shift the focus from customer satisfaction to customer delight.

Originality/value

This study is a pioneering effort to examine the specific circumstances in which service employees’ actions (regardless of in-role or extra-role status) will not produce the desired customer-related outcome in the presence of emotional labor.
Modeling and solving a five-echelon location–inventory–routing problem for red meat supply chain
Authors: Rahbari Misagh , Razavi Hajiagha Seyed Hossein , Raeei Dehaghi Mahdi , Moallem Mahmoud , Riahi Dorcheh Farshid
Published: April 2020

Purpose

In this paper, multi-period location–inventory–routing problem (LIRP) considering different vehicles with various capacities has been investigated for the supply chain of red meat. The purpose of this paper is to reduce variable and fixed costs of transportation and production, holding costs of red meat, costs of meeting livestock needs and refrigerator rents.

Design/methodology/approach

The considered supply chain network includes five echelons. Demand considered for each customer is approximated as deterministic using historical data. The modeling is performed on a real case. The presented model is a linear mixed-integer programming model. The considered model is solved using general algebraic modeling system (GAMS) software for data set of the real case.

Findings

A real-world case is solved using the proposed method. The obtained results have shown a reduction of 4.20 per cent in final price of red meat. Also, it was observed that if the time periods changed from month to week, the final cost of meat per kilogram would increase by 43.26 per cent.

Originality/value

This paper presents a five-echelon LIRP for the meat supply chain in which vehicles are considered heterogeneous. To evaluate the capability of the presented model, a real case is solved in Iran and its results are compared with the real conditions of a firm, and the rate of improvement is presented. Finally, the impact of the changed time period on the results of the solution is examined.
A study on the process and mechanism of social enterprise’s legitimation
Authors: Xu Siqi , Xi Youmin
Published: April 2020

Purpose

This paper aims to explore the complete process and underlying mechanism that social enterprises obtain legitimacy during interactions with stakeholders from theoretical integration of institutional theory and organization ecology perspective.

Design/methodology/approach

Based on theoretical classification, this paper selects six typical Chinese social enterprises and conducts a multi-case analysis.

Findings

The study finds that social enterprises aim at legitimizing single entity or industry and shaping stakeholders’ cognitive boundary simultaneously. Therefore, by adopting constrained cooperation and competition activities, social enterprises use normative isomorphism to achieve personal legitimation and combining ecological niche construction, social enterprises achieve organizational legitimation. By adopting fragmented cooperation-dominant or competition-dominant activities, social enterprises use mimic isomorphism supplemented by competitive isomorphism or population structure creation to obtain industry legitimation. By adopting dynamically integrated coopetition activities, social enterprises use mimic isomorphism and reflexive isomorphism to reach field legitimation.

Originality/value

This paper proposes a mechanism model that the coopetition with stakeholders influences the legitimation process, identifies four stages of social enterprise’s legitimation process and the types of legitimacy obtained in each stage and fills the gap of Chinese indigenous social enterprise research.
Multiple trait dimensions mediate stress gradient effects on plant biomass allocation, with implications for coastal ecosystem services
Authors: De Battisti Davide , Fowler Mike S. , Jenkins Stuart R. , Skov Martin W. , Bouma Tjeerd J. , Neyland Penelope J. , Griffin John N.
Published: April 2020

The plant economic spectrum (PES) predicts a suite of correlated traits in a continuum from resource conservation to rapid resource acquisition. In addition to competing for resources, plants need to cope with other environmental stresses to persist and reproduce. Yet, it is unclear how multiple strategies (i.e. traits uncorrelated with the PES) affect plant biomass allocation, hindering our ability to connect environmental gradients to ecosystem services.

We examined intraspecific dimensionality of leaf and root traits in the salt marsh pioneer species Spartina anglica across salinity, redox and sand content gradients, and related them to above‐ground and below‐ground plant biomass—properties associated with wave attenuation and sediment stabilization in coastal marshes.

Through principal component analysis, we did not find support for a single PES trait dimension (strategy), but instead identified four trait dimensions: (a) leaf economic spectrum (LES, leaf analogue of PES); (b) fine roots‐rhizomes; (c) coarse roots; and (d) salt extrusion. Structural equation modelling showed a shift towards the conservative side of the LES under increasing salinity, while redox had a positive influence on the coarse roots dimension. In turn, these trait dimensions were strongly associated with above‐ground and below‐ground biomass (BLW biomass) allocation.

These results indicate that under high salinity, plants will adopt a conservative strategy and will invest more in BLW biomass. Yet, high sediment redox would still allow plants to invest in above‐ground biomass. Therefore, plants' trait‐mediated biomass allocation depends on the specific combination of abiotic factors experienced at the local scale.

Synthesis. Our study highlights the importance of considering multiple ecological strategies for understanding the effect of the environment on plants. Abiotic stresses can influence multiple trait strategy‐dimensions, with consequences for ecosystem functioning.
Milk products fermented byLactobacillusstrains modulate the gut–bone axis in an ovariectomised murine model
Authors: Eor Ju Young , Tan Pei Lei , Son Yoon Ji , Lee Chul Sang , Kim Sae Hun
Published: April 2020

Limited information is available regarding the effect of Lactobacillus on the gut–bone axis. We examined whether 10‐week administration of milk products fermented by Lactobacillus fermentum MF27 and/or Lactobacillus casei 393 modified gut–bone dysbiosis induced by ovariectomy and lipopolysaccharide (OVX‐LPS) in rats. The fermented milk products selectively modulated gut microbiota composition and improved intestinal barrier function; they suppressed osteoclastogenesis, thereby increasing trabecular bone volume in OVX‐LPS rats. These findings suggest that the gut–bone axis can be modulated not only by viable Lactobacillus strains but also by milk products fermented by Lactobacillus, which may contain metabolites and/or bioactive peptides.
Detecting invertebrate ecosystem service providers in orchards: traditional methods versus barcoding of environmental DNA in soil
Authors: Todd Jacqui H. , Simpson Robert M. , Poulton Joanne , Barraclough Emma I. , Villsen Kurt , Brooks Amber , Richards Kate , Jones Dan
Published: April 2020

The objective of this study was to assess barcoding of environmental DNA as a method for monitoring invertebrate ecosystem service providers in soil samples.

We selected 26 invertebrate ecosystem service providers that occur in New Zealand kiwifruit or apple orchards and produced mitochondrial cytochrome c oxidase gene subunit I (cytochrome oxidase I) and/or 28S ribosomal DNA sequences for each. Specific barcode primers were designed for each invertebrate ecosystem service provider and tested, along with generic barcoding cytochrome oxidase I primers, for their ability to detect DNA from invertebrate ecosystem service providers that had been added to sterilized and unsterilized soil samples.

Although the specific primers accurately detected the invertebrate ecosystem service providers in more than 96% of the samples, the generic cytochrome oxidase I primers detected only 37% of the invertebrate ecosystem service providers added to the sterilized samples and 2.5% in the unsterilized samples.

In a field test, we compared metabarcoding with traditional invertebrate trapping methods to detect the invertebrate ecosystem service providers in 10 kiwifruit and 10 apple orchards. All invertebrate ecosystem service providers were collected in traps in at least one orchard, but very few were identified by metabarcoding of soil environmental DNA.

Although the specific primers can be used as a tool for monitoring invertebrate ecosystem service providers in soil samples, methodological improvements are needed before metabarcoding of soil environmental DNA can be used to monitor these taxa.
Transition of Patients with Opioid Use Disorder from Buprenorphine to Extended‐Release Naltrexone: A Randomized Clinical Trial Assessing Two Transition Regimens
Authors: Comer Sandra D. , Mannelli Paolo , Alam Danesh , Douaihy Antoine , Nangia Narinder , Akerman Sarah C. , Zavod Abigail , Silverman Bernard L. , Sullivan Maria A.
Published: April 2020

Background and Objective

When patients seek to discontinue buprenorphine (BUP) treatment, monthly injectable extended‐release naltrexone (XR‐NTX) may help them avoid relapse. The efficacy of low ascending doses of oral NTX vs placebo for patients transitioning from BUP to XR‐NTX is evaluated in this study.

Methods

In a phase 3, hybrid residential/outpatient study, clinically stable participants with opioid use disorder (N = 101), receiving BUP for more than or equal to 3 months and seeking antagonist treatment, were randomized (1:1) to 7 residential days of descending doses of BUP and low ascending doses of oral NTX (NTX/BUP, n = 50) or placebo (PBO‐N/BUP, n = 51). Both groups received standing ancillary medications and psychoeducational counseling. Following negative naloxone challenge, participants received XR‐NTX (day 8). The primary endpoint was the proportion of participants who received and tolerated XR‐NTX.

Results

There was no statistical difference between groups for participants receiving a first dose of XR‐NTX: 68.6% (NTX/BUP) vs 76.0% (PBO‐N/BUP; P = .407). The mean number of days with peak Clinical Opiate Withdrawal Scale (COWS) score less than or equal to 12 during the treatment period (days 1‐7) was similar for NTX/BUP and PBO‐N/BUP groups (5.8 vs 6.3; P = .511). Opioid withdrawal symptoms during XR‐NTX induction and post‐XR‐NTX observation period (days 8‐11) were mild and similar between groups (mean peak COWS score: NTX/BUP, 5.1 vs PBO‐N/BUP, 5.4; P = .464). Adverse events were mostly mild/moderate.

Conclusions and Scientific Significance

Low ascending doses of oral NTX did not increase induction rates onto XR‐NTX compared with placebo. The overall rate of successful induction across treatment groups supports a brief BUP taper with standing ancillary medications as a well‐tolerated approach for patients seeking transition from BUP to XR‐NTX. (Am J Addict 2020;00:00–00)
Characterization of amoxicillin and clavulanic acid specific T‐cell clones from patients with immediate drug hypersensitivity
Authors: Ariza Adriana , Fernández‐Santamaría Rubén , Meng Xiaoli , Salas María , Ogese Monday O. , Tailor Arun , Bogas Gádor , Torres María José , Naisbitt Dean J.
Published: April 2020

Background

Betalactam (BL) antibiotics are the most common cause of drug hypersensitivity. Amoxicillin (AX), which is often prescribed alongside clavulanic acid (Clav), is the most common elicitor. The aim of this study was to determine whether AX and Clav‐responsive T‐cells are detectable in patients with immediate hypersensitivity to AX‐Clav, to assess whether these T‐cells display the same specificity as that detected in skin and provocation testing, and to explore T‐cell activation pathways.

Methods

Drug‐specific T‐cell clones were generated from immediate hypersensitive patients´ blood by serial dilution and repetitive mitogen stimulation. Antigen specificity was assessed by measurement of proliferation and cytokine release. CD4+/CD8+ phenotype and chemokine receptor expression were analyzed by flow cytometry.

Results

110 AX‐specific and 96 Clav‐specific T‐cell clones were generated from seven patients with positive skin test to either AX or Clav. Proliferation of AX‐ and Clav‐specific clones was dose‐dependent, and no cross‐reactivity was observed. AX‐ and Clav‐specific clones required antigen‐presenting cells to proliferate, and drugs were presented to CD4+ and CD8+ T‐cells by MHC class‐II and I, respectively. A higher secretion of IL‐13 and IL‐5 was detected in presence of the culprit drug compared with the alternative drug. Clones expressed CD69, CCR4, CXCR3, and CCR10.

Conclusions

Our study details the antigen specificity and phenotype of T‐cell clones generated from patients with AX‐Clav‐induced immediate hypersensitivity diagnosed by positive skin test. AX‐ and Clav‐specific clones were generated from patients irrespective of whether AX or Clav was the culprit, although differences in cytokine secretion were observed.
The usefulness of MRI Classification System (MRICS) in a cerebral palsy cohort
Authors: Nagy Eszter , Herbert Zsuzsanna , Péter István , Csorba Eszter , Skobrák Andrea , Farkas Nelli , Hollódy Katalin
Published: April 2020

Aim

Our aim was to investigate perinatal and clinical factors associated with children with cerebral palsy (CP) using magnetic resonance imaging (MRI). The distribution of MRI patterns was based on the MRI classification system (MRICS). Associations between perinatal/clinical characteristics and MRI patterns were also investigated.

Methods

A population‐based cohort study was performed; those 257 children (58.0% male) were enrolled from our CP database who born between 1990 and 2015 in Southwest Hungary and had at least one MRI scan.

Results

Brain maldevelopments were found in 18.7% of our patients, 83.7% of those born at term. Grey matter lesions were found in 19.8% of our patients, and 80.0% of those children were born at term. The rate of white matter injuries was the highest (35.4%); 69.0% of these patients were born before 37th week of gestation. MRI revealed no abnormalities in 13.6% of children with CP. The best values of gross/fine motor and cognitive function tests were found in children with normal MRI and with grey matter injuries. The prevalence of epilepsy was above 60% in every group with an abnormal MRI.

Conclusion

MRI results were conclusive in 86.4% of children with CP. It is highly encouraged to perform cranial MRI in every patient with CP.
Case contamination in electronic health records based case‐control studies
Authors: Wang Lu , Schnall Jill , Small Aeron , Hubbard Rebecca A. , Moore Jason H. , Damrauer Scott M. , Chen Jinbo
Published: April 2020

Clinically relevant information from electronic health records (EHRs) permits derivation of a rich collection of phenotypes. Unlike traditionally designed studies where scientific hypotheses are specified a priori before data collection, the true phenotype status of any given individual in EHR‐based studies is not directly available. Structured and unstructured data elements need to be queried through preconstructed rules to identify case and control groups. A sufficient number of controls can usually be identified with high accuracy by making the selection criteria stringent. But more relaxed criteria are often necessary for more thorough identification of cases to ensure achievable statistical power. The resulting pool of candidate cases consists of genuine cases contaminated with noncase patients who do not satisfy the control definition. The presence of patients who are neither true cases nor controls among the identified cases is a unique challenge in EHR‐based case‐control studies. Ignoring case contamination would lead to biased estimation of odds ratio association parameters. We propose an estimating equation approach to bias correction, study its large sample property, and evaluate its performance through extensive simulation studies and an application to a pilot study of aortic stenosis in the Penn medicine EHR. Our method holds the promise of facilitating more efficient EHR studies by accommodating enlarged albeit contaminated case pools.
Developmental trajectories of event centrality and socio‐emotional well‐being after transition to high school
Authors: Iimura Shuhei
Published: April 2020

Although the transition from junior high or middle school to high school can be a stressful turning point for youth socio‐emotional development, the role of individual differences in susceptibility to the transition in adolescents’ socio‐emotional well‐being remains unclear. The current study examined the developmental relation between how central the high school transition is to a student’s identity or life course (i.e., event centrality) and socio‐emotional well‐being after transition. High school students, including cohorts in tenth to twelveth grade (n = 2,265, Mage at Time 1 = 15.9 years, SDage = 0.9 years), participated in a four‐wave longitudinal survey for a year and completed questionnaires assessing event centrality and socio‐emotional well‐being. Latent growth curve modelling revealed individual differences in the developmental trajectory of event centrality regarding high school transition across the tenth to twelveth grades. Increase in the centrality of transition was closely associated with improvement in socio‐emotional well‐being for each grade progression. Findings highlight the value of examining individual differences in the degree to which the school transition becomes a turning point in a student’s identity or life course.

Statement of contribution

What is already known on the subject?

Adolescents’ socio‐emotional well‐being decreases on average after school transition.

Event centrality, how central the transition is to student identity, is related to socio‐emotional well‐being.

No study has examined event centrality and well‐being after transition longitudinally.

What the present study adds?

Individual differences exist in the development of event centrality across grades 10–12.

Increased event centrality of transition is associated with improved socio‐emotional well‐being.

Development researchers must consider individual differences in susceptibility to the transition.
Tumor‐associated macrophage interleukin‐β promotes glycerol‐3‐phosphate dehydrogenase activation, glycolysis and tumorigenesis in glioma cells
Authors: Lu Jian , Xu Zhongye , Duan Hubin , Ji Hongming , Zhen Zigang , Li Bo , Wang Huangsuo , Tang Huoquan , Zhou Jie , Guo Tao , Wu Bin , Wang Dawei , Liu Yueting , Niu Yuhu , Zhang Ruisheng
Published: April 2020

Tumor‐immune crosstalk within the tumor microenvironment (TME) occurs at all stages of tumorigenesis. Tumor‐associated M2 macrophages play a central role in tumor development, but the molecular underpinnings have not been fully elucidated. We demonstrated that M2 macrophages produce interleukin 1β (IL‐1β), which activates phosphorylation of the glycolytic enzyme glycerol‐3‐phosphate dehydrogenase (GPD2) at threonine 10 (GPD2 pT10) through phosphatidylinositol‐3‐kinase‐mediated activation of protein kinase‐delta (PKCδ) in glioma cells. GPD2 pT10 enhanced its substrate affinity and increased the catalytic rate of glycolysis in glioma cells. Inhibiting PKCδ or GPD2 pT10 in glioma cells or blocking IL‐1β generated by macrophages attenuated the glycolytic rate and proliferation of glioma cells. Furthermore, human glioblastoma tumor GPD2 pT10 levels were positively correlated with tumor p‐PKCδ and IL‐1β levels as well as intratumoral macrophage recruitment, tumor grade and human glioblastoma patient survival. These results reveal a novel tumorigenic role for M2 macrophages in the TME. In addition, these findings suggest possible treatment strategies for glioma patients through blockade of cytokine crosstalk between M2 macrophages and glioma cells.
How to study intertwined and autoregulated eukaryotic signal transduction pathways
Authors: Heinisch Jürgen J.
Published: April 2020

Mitogen‐activated protein kinase (MAPK) pathways are a major means of eukaryotic cells to adapt to environmental changes, in the case of microorganisms, and to nutritional and hormonal signals, in the case of multicellular organisms. Numerous defects in such architecturally conserved pathways have been associated with different human cancers. These signaling cascades usually commence with sensors located in the plasma membrane, which through specific protein kinases activate a conserved tripartite MAPK module. Phosphorylation of their targets, that is, cytosolic proteins and/or transcription factors, then triggers the proper cellular response. In the model yeast Saccharomyces cerevisiae and other fungi, the cell wall integrity pathway (CWI) has been extensively studied and its components may serve as targets for antifungal drugs of clinical and agricultural importance. Another well‐known MAPK cascade, the high osmolarity glycerol (HOG) pathway, is required to cope with osmotic stress. In the past decade, it has become increasingly evident that such pathways do not act in a linear top‐down fashion, but are highly regulated by internal feedback mechanisms as well as by cross‐pathway interactions. The work of Jiménez‐Gutiérrez et al. in this issue provides an elegant way to identify new players in these complex networks.

Comment on: https://doi.org/10.1111/febs.15288