bluuebunny/crossref_metadata_2025_split huggingface dataset:
The MLO1 powdery mildew susceptibility gene in Lathyrus species: The power of high‐density linkage maps in comparative mapping and synteny analysis
Authors: Santos Carmen , Polanco Carlos , Rubiales Diego , Vaz Patto Maria Carlota 
Published: May 2021

AbstractPowdery mildews are major diseases for a range of crops. The loss of function of specific Mildew Locus O (MLO) genes has long been associated with pre‐haustorial plant resistance to powdery mildew and has proven to be durable in several species. Erysiphe pisi is the major causal agent of powdery mildew in pea (Pisum sativum L.) and in the closely related Lathyrus sativus L. and Lathyrus cicera L. PsMLO1 has been extensively studied in pea. However, no MLO gene family members have been isolated and characterized in Lathyrus species so far. In this study, MLO1 genes were isolated and characterized in L. sativus and L. cicera genotypes with varied levels of partial resistance against powdery mildew. Phylogenetic analyses confirmed that Lathyrus MLO1 belongs to Clade V, like all dicot MLO proteins associated with powdery mildew susceptibility. A L. sativus recombinant inbred line population (RIL) was genotyped by sequencing to develop a high‐density L. sativus genetic linkage map. DNA sequence polymorphisms between the analyzed genotypes allowed the location of MLO1 in the newly developed L. sativus RIL genetic linkage map. Subsequent comparative mapping between L. sativus and L. cicera genetic maps and P. sativum, Lens culinaris Medik., and Medicago truncatula Gaertn. reference genomes revealed important aspects of the conservation of the MLO1 locus position and of the overall chromosomal rearrangements occurring during legume evolution, with relevance to legume disease resistance breeding programs.
Status of the Implementation of Industry 4.0 in SMEs and Framework for Smart Manufacturing
Authors: Rauch Erwin , Matt Dominik T. 
Published: May 2021

AbstractIn this chapter, we explore after 10 years of Industry 4.0 the status of the application in manufacturing companies and especially in small- and medium-sized enterprises (SMEs). Based on literature and previously conducted research we present guidelines and a modular framework for implementing smart manufacturing in SMEs. In addition, a stage model is illustrated to support SMEs in breaking down the framework from a design level to an implementation and operational level. Finally, an outlook is given on the future challenges that SMEs will face in the coming years when they want to reach the next level of Industry 4.0 in their own company.
Toward SME 4.0: The Impact of Industry 4.0 Technologies on SMEs’ Business Models
Authors: Sauer Philipp C. , Orzes Guido , Davi Laura 
Published: May 2021

Abstract
Industry 4.0 (I4.0) transforms current production paradigms and raises an inherent need to integrate this with a firm’s rational of creating, delivering, and capturing value, i.e., the business model. The resource intensive I4.0 technology implementation challenges any organization and especially small- and medium-sized enterprises (SMEs). To provide theoretical and practical support for this, our chapter first conducts a systematic literature review on business models and I4.0 technologies with a qualitative investigation and a quantitative contingency analysis. The chapter then analyses secondary data from 30 SMEs of an innovative Italian manufacturing cluster for which business model elements are modified while implementing specific I4.0 technologies. To guide future practice and research, 13 propositions and 4 research directions are developed on how implementing individual I4.0 technologies can modify specific business model elements for SMEs 4.0.
Implementation Strategies for SME 4.0: Insights on Thailand
Authors: Sopadang Apichat , Ramingwong Sakgasem , Anantana Tanyanuparb , Tamvimol Krisana 
Published: May 2021

AbstractThis chapter presents how SMEs or companies can implement Industry 4.0 based on case studies in Thai SMEs. Additionally, the chapter examined implementation strategies to convert a company successfully to SME 4.0. The implementation process includes identifying business trends, foresight strategy, gap analysis, industrial research and capacity development, and technology blueprint development plan. By working closely as the triple helix with universities and tech-development agencies, the inside-out and outside-in approaches are used. There can be several challenges during the implementation, such as the requirement of new skills, new technology, and investment needs. The challenges can be addressed by setup and implement the appropriate strategy for developing workers’ skill sets, making investments in the new technologies, and improving the efficiency of the production process.
Readiness Model for Integration of ICT and CPS for SMEs Smart Logistics
Authors: Ramingwong Sakgasit , Ramingwong Lachana , Thaiupathump Trasapong , Chompu-inwai Rungchat 
Published: May 2021

AbstractAlthough it is an extremely important step to gain sustained competitive advantage in the era of Industry 4.0, the integration of Information and Communication Technology (ICT) and Cyber-Physical Systems (CPS) for smart logistics can be challenging. In order to successfully implement such technologies, it is crucial, particularly for SMEs, to self-evaluate their own readiness for integrating technologies for smart logistics. This research proposes a readiness model which can be used as a guideline before implementing technologies for smart logistics at the SMEs level. It describes essential elements in the integration of ICT and CPS for smart logistics, as well as the potential five stages of implementation, which are initial, trial, organized, automated, and optimized.
A Case Study: Industry 4.0 and Human Factors in SMEs
Authors: Zsifkovits Helmut , Woschank Manuel , Pacher Corina 
Published: May 2021

AbstractThere is a number of barriers for smaller companies when starting the journey toward Industry 4.0. When implementing new technology and processes, there are often strong mental barriers from people that have been doing the work in a certain manner over the years. In addition to technological challenges, organizational adaptations are required, and a change in mindsets. Using the case of one machining services company, the implementation scenario is described, with the steps necessary to ensure an effective implementation of new technology. The management of visibility is critical for the adoption and success of new systems. Neglecting the human factor will inevitably result in failure. Derived from the case, the chapter draws some conclusions for Industry 4.0 implementation in SMEs in a human-centered manner.
Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin
Authors: Reid Laura J. , Gibb Fraser W. , Colhoun Helen , Wild Sarah H. , Strachan Mark W. J. , Madill Karen , Dhillon Baljean , Forbes Shareen 
Published: May 2021

Abstract
Aims/hypothesis
We aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI).

Methods
This is a retrospective cohort study using the Scottish Care Information – Diabetes database for retinal screening outcomes and HbA1c changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan–Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA1c, blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA1c and change in HbA1c on diabetic retinopathy progression was assessed within CSII and MDI cohorts.

Results
CSII participants were significantly younger, were from less socially deprived areas, and had lower HbA1c and higher diastolic BP at baseline. There was a larger reduction in HbA1c at 1 year in those on CSII vs MDI (−6 mmol/mol [−0.6%] vs −2 mmol/mol [−0.2%], p < 0.01). Diabetic retinopathy progression occurred in a smaller proportion of adults following commencement of CSII vs continued MDI therapy over mean 2.3 year follow-up (26.5% vs 18.6%, p = 0.0097). High baseline HbA1c (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA1c at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group.

Conclusions/interpretation
CSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA1c. Progression of diabetic retinopathy over 3 years was not associated with a change in HbA1c.

Graphical abstract
Great-tailed Grackles (Quiscalus mexicanus) as Biomonitors of Atmospheric Heavy Metal Pollution in Urban Areas of Monterrey, Mexico
Authors: Guzmán-Velasco Antonio , Ramírez-Cruz Javier I. , Ruiz-Aymá Gabriel , Rodríguez-Sánchez Iram P. , Garza-Ocañas Lourdes , Treviño-Alvarado Victor M. , González-Rojas José I. , Olalla-Kerstupp Alina 
Published: May 2021

AbstractHeavy metals exposure has been linked to severe health problems. In Mexico, the Monterrey metropolitan area (MMA) is considered one of the most polluted industrial regions. Because birds have been used successfully as environmental biomonitors, the levels of lead, cadmium, and arsenic in feathers of Great-tailed grackles (Quiscalusmexicanus) from two sites within and one site outside the MMA were determined. One hundred birds were captured, samples were analyzed by atomic absorption spectrometry. Ciudad Universitaria had the highest mean values of lead and cadmium, 11.91 ppm d.w. and 1.66 ppm d.w., respectively. This was at least, 10- and 8-times higher than the two other sample sites. We believe that using Great-tailed grackles as bioindicators in conjunction with air pollutants sampling from meteorological stations in Monterrey City could help in making decisions when applying environmental remediation measures as well as in the selection of places for housing, school and work among others.
Influence of process parameters for sheet lamination based on laser micro-spot welding of austenitic stainless steel sheets for bone tissue applications
Authors: Cedeño-Viveros Luis D. , Vázquez-Lepe Elisa , Rodríguez Ciro A. , García-López Erika 
Published: May 2021

AbstractThe laser micro-spot welding process was studied to implement a sheet lamination process-based methodology for the fabrication of austenitic stainless steel scaffolds. AISI 302 sheets with a thickness of 254 μm were laser cut and laser welded. Experimental tests were carried out with different values of average laser power (i.e., 180, 200, and 220 W) and different exposure times (25, 50, 75, 100, 125 ms). The micro-spot welds were visually inspected according to the ISO 13919-1 Class B requirements. Spot welds were qualitatively characterized, and weld dimensions were measured (i.e., penetration depth, top, middle, and bottom width and the heat-affected zone (HAZ)) to identify the cross-sectional shape. Furthermore, process efficiencies (i.e., coupling, melting, and process) were studied. A seam welding model was adapted to calculate the required exposure time and was used to obtain a micro-spot weld to accomplish the quality requirements of the scaffold. A scaffold prototype was designed and manufactured using the selected parameters by experimental trials and using the mathematical model (i.e., a laser power of 220 W and an exposure time of 45 ms).
Impact of intravenous alteplase on sub-angiographic emboli in high-resolution diffusion-weighted imaging following successful thrombectomy
Authors: Broocks Gabriel , Meyer Lukas , Kabiri Reza , Kniep Helge C. , McDonough Rosalie , Bechstein Matthias , van Horn Noel , Lindner Thomas , Sedlacik Jan , Cheng Bastian , Thomalla Götz , Schön Gerhard , Fiehler Jens , Hanning Uta , Schönfeld Michael H. 
Published: May 2021

Abstract
Objective
Thrombus microfragmentation causing peripheral emboli (PE) during mechanical thrombectomy (MT) may modulate treatment effects, even in cases with successful reperfusion. This study aims to investigate whether intravenous alteplase is of potential benefit in reducing PE after successful MT.

Methods
Patients from a prospective study treated at a tertiary care stroke center between 08/2017 and 12/2019 were analyzed. The main inclusion criterion was successful reperfusion after MT (defined as expanded thrombolysis in cerebral infarction (eTICI) scale ≥ 2b50) of large vessel occlusion anterior circulation stroke. All patients received a high-resolution diffusion-weighted imaging (DWI) follow-up 24 h after MT for PE detection. Patients were grouped as “direct MT” (no alteplase) or as MT plus additional intravenous alteplase. The number and volume of ischemic core lesions and PE were then quantified and analyzed.

Results
Fifty-six patients were prospectively enrolled. Additional intravenous alteplase was administered in 46.3% (26/56). There were no statistically significant differences of PE compared by groups of direct MT and additional intravenous alteplase administration regarding mean numbers (12.1, 95% CI 8.6–15.5 vs. 11.1, 95% CI 7.0–15.1; p = 0.701), and median volume (0.70 mL, IQR 0.21–1.55 vs. 0.39 mL, IQR 0.10–1.62; p = 0.554). In uni- and multivariable linear regression analysis, higher eTICI scores were significantly associated with reduced PE, while the administration of alteplase was neither associated with numbers nor volume of peripheral emboli. Additional alteplase did not alter reperfusion success.

Conclusions
Intravenous alteplase neither affects the number nor volume of sub-angiographic DWI-PE after successful endovascular reperfusion. In the light of currently running randomized trials, further studies are warranted to validate these findings.

Key Points
• Thrombus microfragmentation during endovascular stroke treatment may cause peripheral emboli that are only detectable on diffusion-weighted imaging and may directly compromise treatment effects.
• In this prospective study, the application of intravenous alteplase did not influence the occurrence of peripheral emboli detected on high-resolution diffusion-weighted imaging.
• A higher degree of recanalization was associated with a reduced number and volume of peripheral emboli and better functional outcome, while contrariwise, peripheral emboli did not modify the effect of recanalization on modified Rankin Scale scores at day 90.
Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn’s disease-associated small bowel carcinoma
Authors: Arpa Giovanni , Vanoli Alessandro , Grillo Federica , Fiocca Roberto , Klersy Catherine , Furlan Daniela , Sessa Fausto , Ardizzone Sandro , Sampietro Gianluca , Macciomei Maria Cristina , Nesi Gabriella , Tonelli Francesco , Capella Carlo , Latella Giovanni , Ciardi Antonio , Caronna Roberto , Lenti Marco Vincenzo , Ciccocioppo Rachele , Barresi Valeria , Malvi Deborah , D’Errico Antonietta , Rizzello Fernando , Poggioli Gilberto , Mescoli Claudia , Rugge Massimo , Luinetti Ombretta , Paulli Marco , Di Sabatino Antonio , Solcia Enrico 
Published: May 2021

AbstractMost Crohn’s disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies.
Teaching and assessing intra-operative consultations in competency-based medical education: development of a workplace-based assessment instrument
Authors: Gomes Marcio M. , Driman David , Park Yoon Soo , Wood Timothy J. , Yudkowsky Rachel , Dudek Nancy L. 
Published: May 2021

AbstractCompetency-based medical education (CBME) is being implemented worldwide. In CMBE, residency training is designed around competencies required for unsupervised practice and use entrustable professional activities (EPAs) as workplace “units of assessment”. Well-designed workplace-based assessment (WBA) tools are required to document competence of trainees in authentic clinical environments. In this study, we developed a WBA instrument to assess residents’ performance of intra-operative pathology consultations and conducted a validity investigation. The entrustment-aligned pathology assessment instrument for intra-operative consultations (EPA-IC) was developed through a national iterative consultation and used clinical supervisors to assess residents’ performance at an anatomical pathology program. Psychometric analyses and focus groups were conducted to explore the sources of evidence using modern validity theory: content, response process, internal structure, relations to other variables, and consequences of assessment. The content was considered appropriate, the assessment was feasible and acceptable by residents and supervisors, and it had a positive educational impact by improving performance of intra-operative consultations and feedback to learners. The results had low reliability, which seemed to be related to assessment biases, and supervisors were reluctant to fully entrust trainees due to cultural issues. With CBME implementation, new workplace-based assessment tools are needed in pathology. In this study, we showcased the development of the first instrument for assessing resident’s performance of a prototypical entrustable professional activity in pathology using modern education principles and validity theory.
Integrated analysis of programmed cell death ligand 1 expression reveals increased levels in high-grade glioma
Authors: Hölzl Dorothee , Hutarew Georg , Zellinger Barbara , Schlicker Hans U. , Schwartz Christoph , Winkler Peter A. , Sotlar Karl , Kraus Theo F. J. 
Published: May 2021

Abstract
Purpose
Gliomas are the most frequent primary brain tumors of adults. Despite intensive research, there are still no targeted therapies available. Here, we performed an integrated analysis of glioma and programmed cell death ligand 1 (PD-L1) in 90 samples including 58 glioma and 32 control brain tissues.

Methods
To identify PD-L1 expression in glioma, we performed immunohistochemical analysis of PD-L1 tumor proportion score (TPS) using the clinically valid PD-L1 22C3 antibody on 90 samples including controls and WHO grade I–IV gliomas.

Results
We found that PD-L1 is highly expressed in a subfraction of glioma cells. Analysis of PD-L1 levels in different glioma subtypes revealed a strong intertumoral variation of PD-L1 protein. Furthermore, we correlated PD-L1 expression with molecular glioma hallmarks such as MGMT-promoter methylation, IDH1/2 mutations, TERT promoter mutations and LOH1p/19q.

Conclusion
In summary, we found that PD-L1 is highly expressed in a subfraction of glioma, indicating PD-L1 as a potential new marker in glioma assessment opening up novel therapeutic approaches.
Prevalence of Alaria alata mesocercariae in wild boars from Brandenburg, Germany
Authors: Kästner Carolyn , Bier Nadja Seyhan , Mayer-Scholl Anne , Nöckler Karsten , Richter Martin Heinrich , Johne Annette 
Published: May 2021

AbstractSince 2002, Alaria (A.) alata mesocercariae (AM) have been found during routine Trichinella inspection of wild boars in many European countries. To date, human infection with AM through consumption of undercooked or raw AM infested wild boar meat cannot be excluded. In Germany, data on the parasite’s prevalence in wild boars are scarce. To better understand temporal and spatial fluctuations of this parasite, this study investigated the prevalence of AM in wild boars in the German federal state of Brandenburg during three hunting seasons from 2017 to 2020. In total, 28.3% (100/354, 95% CI: 23.3–33.3%) of all wild boars sampled in eight counties of Brandenburg were tested positive for AM by Alaria alata mesocercariae migration technique (AMT). AM were detected in wild boars from seven different counties. Samples from one county (Havelland) tested completely negative for AM (0/16). Prevalences of the seven AM positive counties of Brandenburg ranged from 11.5 (3/26, 95% CI: 2.5–30.1%) in Märkisch-Oderland to 64.1% (25/39, 95% CI: 47.2–78.8%) in Uckermark. An association between sex and A. alata positivity could not be determined. A statistically significant increase in frequency of older AM positive wild boars was observed (p = 0.001). For a nationwide assessment of the prevalence of A. alata in wild boars and the risk for consumers of ingesting viable AM by consumption of raw or undercooked AM infested wild boar meat, further long-term studies in different regions of Germany are needed.