bluuebunny/crossref_metadata_2025 huggingface dataset:
Dendrite regeneration in C. elegansis controlled by the RAC GTPase CED-10 and the RhoGEF TIAM-1
Authors: Brar Harjot Kaur , Dey Swagata , Bhardwaj Smriti , Pande Devashish , Singh Pallavi , Dey Shirshendu , Ghosh-Roy Anindya
Published: July 2021

Neurons are vulnerable to physical insults which compromise the integrity of both dendrites and axons. Although several molecular pathways of axon regeneration are identified, our knowledge of dendrite regeneration is limited. To understand the mechanisms of dendrite regeneration, we used PVD neurons in C. elegans having stereotyped branched dendrites. Using femtosecond laser, we severed the primary dendrites and axon of this neuron. After severing the primary dendrites near the cell body, we observed sprouting of new branches from the proximal site within 6 hours, which regrew further with timein an unstereotyped manner.This was accompanied by reconnection between the proximal and distal dendrites as well as the fusion among the higher-order branches as reported before. We quantified the regeneration pattern in threeaspects –territory length, number of branchesand fusion phenomena.Axonal injury causes a retraction of the severed end followed by a Dual leucine zipper kinase-1 (DLK-1) dependent regrowth from the severed end.We tested the roles of the major axon regenerationsignaling hubs such as DLK-1-RPM-1, cAMP elevation, let-7 miRNA, AKT-1, Phosphatidyl serine exposure/PS in dendrite regeneration. We found that neither regrowth nor fusionis affected by the axon injury pathway molecules. Surprisingly, we found that the RAC GTPase CED-10and its upstream GEF TIAM-1 play a cell-autonomous role in dendrite regeneration. Additionally, function of CED-10 in epidermal cell is critical for post-dendrotomy fusion phenomena. This work describes a novel regulatory mechanism of dendrite regeneration andprovides a framework for understanding the cellular mechanism of dendrite regeneration using PVD neuron as a model system.
FISH-quant v2: a scalable and modular analysis tool for smFISH image analysis
Authors: Imbert Arthur , Ouyang Wei , Safieddine Adham , Coleno Emeline , Zimmer Christophe , Bertrand Edouard , Walter Thomas , Mueller Florian
Published: July 2021

Regulation of RNA abundance and localization is a key step in gene expression control. Single-molecule RNA fluorescence in-situ hybridization (smFISH) is a widely used single-cell-single-molecule imaging technique enabling a quantitative understanding of gene expression and its regulatory mechanisms. Recent progress in experimental techniques provides larger data-sets, requiring adequate tools for data analysis and exploration. Here, we present FISH-quant v2, a highly modular analysis tool accessible both for non-experts and experts, which we validated and applied on large-scale smFISH image datasets. Our package allows the user to detect isolated and clustered mRNA spots, segment nuclei and cells, quantify RNA localization patterns and visualize these results at the single-cell level.
The SARS-CoV-2 reproduction number R0 in cats
Authors: Gonzales Jose L. , de Jong Mart C.M. , Gerhards Nora M. , Van der Poel Wim H. M.
Published: July 2021

Domestic cats are susceptible to SARS-CoV-2 virus infection and given that they are in close contact with people, assessing the potential risk cats represent for the transmission and maintenance of SARS-CoV-2 is important. Assessing this risk implies quantifying transmission from humans-to-cats, from cats-to-cats and from cats-to-humans. Here we quantified the risk of cat-to-cat transmission by reviewing published literature describing transmission either experimentally or under natural conditions in infected households. Data from these studies were collated to quantify the SARS-CoV-2 reproduction number R0 among cats. The estimated R0 was significantly higher than 1, hence cats could play a role in the transmission and maintenance of SARS-CoV-2. Questions that remain to be addressed are the risk of transmission from humans-to-cats and cats-to-humans. Further data on household transmission and data on virus levels in both the environment around infected cats and their exhaled air could be a step towards assessing these risks.
Imaging biological samples by integrated differential phase contrast (iDPC) STEM technique
Authors: Li Xujing , Lazić Ivan , Huang Xiaojun , Wang Li , Deng Yuchen , Niu Tongxin , Wu Dongchang , Wirix Maarten , Yu Lingbo , Sun Fei
Published: July 2021

Scanning transmission electron microscopy (STEM) is a powerful imaging technique and has been widely used in current material science research. The attempts of applying STEM into biological research have been going on for decades while applications have still been limited because of the existing bottlenecks in dose efficiency and non-linearity in contrast. Recently, integrated differential phase contrast (iDPC) STEM technique emerged and achieved a linear phase contrast imaging condition, while resolving signals of light elements next to heavy ones even at low electron dose. This enables successful investigation of beam sensitive materials. Here, we investigate iDPC-STEM advantages in biology, in particular, chemically fixed and resin embedded biological tissues. By comparing results to the conventional TEM, we have found that iDPC-STEM not only shows better contrast but also resolves more structural details at molecular level, including conditions of extremely low dose and minimal heavy-atom staining. For thick sample sections, iDPC-STEM is particularly advantageous. Unlike TEM, it avoids contrast inversion canceling effects, and by adjusting the depth of focus, fully preserves the contrast of relevant features along with the sample. In addition, using depth-sectioning, iDPC-STEM enables resolving in-depth structural variation. Our work suggests that promising, wide and attractive applications of iDPC-STEM in biological research are opening.
Protein kinase Cδ is essential for the IgG response against T cell-independent type 2 antigens and commensal bacteria
Authors: Fukao Saori , Haniuda Kei , Tamaki Hiromasa , Kitamura Daisuke
Published: July 2021

Antigens (Ags) with multivalent and repetitive structure elicit IgG production in a T cell-independent manner. However, the mechanisms by which such T cell-independent type-2 (TI-2) Ags induce IgG responses remain obscure. Here we report that BCR engagement with a TI-2 Ag but not with a T cell-dependent (TD) Ag was able to induce the transcription ofactivation-induced cytidine deaminase(AID) and efficient class switching to IgG3 upon co-stimulation with IL-1 or IFN-α. TI-2 Ags strongly induced the phosphorylation of protein kinase C (PKC)δ and PKCδ mediated theAIDtranscription through the induction of BATF, the key transcriptional regulator of AID expression. In PKCδ-deficient mice, production of IgG was intact against TD Ag but abrogated against typical TI-2 Ags as well as commensal bacteria, and experimental disruption of the gut epithelial barrier resulted in fatal bacteremia. Thus, our results revealed novel molecular requirements for class-switching in the TI-2 response and highlighted its importance in homeostatic commensal-specific IgG production.
The mitotic spindle protein CKAP2 potently increases formation and stability of microtubules
Authors: McAlear Thomas S. , Bechstedt Susanne
Published: July 2021

Cells increase microtubule dynamics to make large rearrangements to their microtubule cytoskeleton during cell division. Changes in microtubule dynamics are essential for the formation and function of the mitotic spindle, and misregulation can lead to aneuploidy and cancer. Using in vitro reconstitution assays we show that the mitotic spindle protein Cytoskeleton-Associated Protein 2 (CKAP2) has a strong effect on nucleation of microtubules by lowering the critical tubulin concentration 100-fold. CKAP2 increases the apparent rate constant ka of microtubule growth by 50-fold and increases microtubule growth rates. In addition, CKAP2 strongly suppresses catastrophes. Our results identify CKAP2 as the most potent microtubule growth factor to date. These finding help explain CKAP2s role as an important spindle protein, proliferation marker, and oncogene.
A universal framework for detecting cis-regulatory diversity in DNA regions
Authors: Biswas Anushua , Narlikar Leelavati
Published: July 2021

High-throughput sequencing-based assays measure different biochemical activities pertaining to gene regulation, genome-wide. These activities include transcription factor (TF)–DNA binding, enhancer activity, open chromatin, and more. A major goal is to understand underlying sequence components, or motifs, that can explain the measured activity. It is usually not one motif but a combination of motifs bound by cooperatively acting proteins that confers activity to such regions. Furthermore, regions can be diverse, governed by different combinations of TFs/motifs. Current approaches do not take into account this issue of combinatorial diversity. We present a new statistical framework, cisDIVERSITY, which models regions as diverse modules characterized by combinations of motifs while simultaneously learning the motifs themselves. Because cisDIVERSITY does not rely on knowledge of motifs, modules, cell type, or organism, it is general enough to be applied to regions reported by most high-throughput assays. For example, in enhancer predictions resulting from different assays—GRO-cap, STARR-seq, and those measuring chromatin structure—cisDIVERSITY discovers distinct modules and combinations of TF binding sites, some specific to the assay. From protein–DNA binding data, cisDIVERSITY identifies potential cofactors of the profiled TF, whereas from ATAC-seq data, it identifies tissue-specific regulatory modules. Finally, analysis of single-cell ATAC-seq data suggests that regions open in one cell-state encode information about future states, with certain modules staying open and others closing down in the next time point.
A rare case of a 2:2:1 ternary cocrystal of pyridine sulfides and trithiocyanuric acid
Authors: Wzgarda-Raj Kinga , Książkiewicz Olga , Palusiak Marcin
Published: July 2021

We report a rare case of a 2:2:1 ternary cocrystal consisting of two trithiocyanuric acid molecules, two bis(pyridin-4-yl) sulfide molecules and 1,4-bis(pyridin-4-yl)tetrasulfane, namely, 1,3,5-triazinane-2,4,6-trithione–4-(pyridin-4-ylsulfanyl)pyridine–1,4-bis(pyridin-4-yl)tetrasulfane (2/2/1), 2C3H3N3S3·2C10H8N2S·C10H8N2S4. This interesting crystal structure with five neutral molecules per asymmetric unit was synthesized and characterized by means of X-ray diffraction (XRD) experiments and quantum-chemical modelling. Among various specific interactions, hydrogen and halogen bridges have a significant role in stabilizing the crystal structure. In particular, the role played by stacking interactions has been revealed by structure analysis and theoretical calculations. Crystallization was spontaneous and reproducible. One of the components, 1,4-bis(pyridin-4-yl)tetrasulfane, has been characterized by XRD for the first time.
Pricing the EpiPen: This is Going to Sting
Authors: Steenburgh Thomas J. , Hammaker Paul M.
Published: July 2021

This case examines the public controversy that erupted over the increasingly high price of EpiPens. Mylan Inc. (Mylan), a generic drug maker, bought the EpiPen product line from Merck in 2007. Since that time, the company both invested in marketing to raise awareness for the drug and dramatically increased the price, lifting it from $100 to $600 per two pack in the U.S. In 2016, simmering consumer anger about the high prices of pharmaceutical drugs finally reached a boiling point and a media firestorm ensued. The case challenges students to think about the role of fairness in pricing. How can Mylan justify the dramatic price increases? How can it justify the variation in prices across countries, as an EpiPen is priced at an equivalent of $85 in France? The case challenges students to think about how they would handle a public controversy. The EpiPen case is well suited for students in MBA, MBA for Executives, and executive education programs. For MBA students, it can be placed in first-year marketing, pricing, or marketing communications courses. For executives, it can serve as a vehicle to discuss both ethical issues of pricing and how to handle a public controversy.
Pancho’s Burritos
Authors: Dorronsoro Daniel
Published: July 2021

Pancho’s Burritos is a high-end fast-food restaurant located in Charlottesville, Virginia. Due to a recent surge in customers, the lines at the restaurant during peak hours are becoming very long and causing excessive customer waiting. To improve current customer wait times and plan for future growth requirements, Francisco “Pancho” Escoba, the proprietor, wants to get a better understanding of the current operational capacity. The key decision Escoba must make is how to redesign his burrito-making process to increase the capacity and reduce customer wait time.

Suitable for an undergraduate or MBA course, the case can be used in an introductory operations course to teach capacity analysis and queuing. The case provides a relatable and understandable setting for students without an operations background to gain a better grasp of basic course concepts and illustrates how interactions between capacity and queuing affect one another. As an exam or review case it works well because it contains standard process calculations that all students should know how to perform.
The Walt Disney Company: Mickey Mouse Visits Shanghai
Authors: Maiden Stephen , Writer Case , Yemen Gerry , Weiss Elliott N. , Wight Oliver
Published: July 2021

The strategic and tactical problems of managing the operations function in a service environment can be examined through the context of the Walt Disney Company (DIS) opening Shanghai Disneyland. The company and its investors were excited about the Shanghai opening for a good reason: demographics. The resort would be located in the Pudong district of Shanghai, easily the wealthiest of all of China’s districts. A massive 330 million people lived with a three-hour driving radius of the resort site, compared with 19.6 million who lived within the same radius at DIS’s most profitable park, Walt Disney World in Orlando, Florida. Still, risks remained. Construction complications had delayed the opening almost a year longer than expected and cost overruns and alterations had increased the final price tag of the project. The Chinese economy had also hit a rough patch following the Chinese stock market slump in the summer of 2015. With the world watching, could the classic Disney theme park experience be delivered with the right cultural balance to appeal to its largely Chinese customers? Could DIS get it right?
A prospective policy transfer of learning from abroad in funding long-term care in England
Authors: Powell Martin
Published: July 2021

Purpose

This article explores to what extent the long debate in England over the funding of long-term care (LTC) has involved learning from abroad.

Design/methodology/approach

It draws on Mossberger and Wolman’s (2003) framework which proposes criteria for assessing policy transfer as a form of prospective policy evaluation: awareness; assessment and application. The documents examined are the sources cited by the reports that examined funding LTC in England since 1999. The study uses interpretive content analysis in a deductive approach (applying the framework) that focuses on both manifest and latent content.

Findings

It finds that both the reports and the cited studies tend to focus on a fairly narrow range of nations, with most attention on Germany, Japan and Scotland. Most studies broadly do not provide much in the way of a clear rationale, and the level of details provided varies. There is relatively little focus on problems. Aims, objectives and goals are little mentioned in some studies, but they tend to be fairly abstract or “high level.” Similarly, there is limited detail on settings. Finally, only a few studies provide a clear recommendation.

Originality/value

It focuses on the neglected topic of the evidence behind reports which are intended to provide recommendations for policy change. The Mossberger and Wolman’s (2003) framework has been used in a small-scale but appears to be well-suited for this purpose.
Relationships among lean, service quality expectation and performance in hospitals
Authors: Vanichchinchai Assadej
Published: July 2021

Purpose

The purpose of this study is to investigate the links between lean, service quality expectation (SQE) and service quality performance (SQP) in outpatient departments (OPD).

Design/methodology/approach

The measurement instruments were developed from a comprehensive literature review, then verified by experts and confirmatory factor analysis. Multiple responses were applied to improve the reliability of data obtained from 220 Thai hospitals. The hypotheses were tested with linear regression and path analysis of structural equation modeling.

Findings

It was found that lean has significant positive impacts on all SQP dimensions (i.e. tangibility, reliability, responsiveness, assurance and empathy) and on overall SQP. SQE has significant positive direct effects on lean and SQP, and has a significant positive indirect effect on SQP through lean.

Originality/value

This is one of the first examples of research to present insights into the relationships between lean, SQE and SQP in OPD.
Linking knowledge development with sustainable supply chain performance: mediating effects of innovativeness, proactiveness and risk taking
Authors: Tipu Syed Awais Ahmad , Fantazy Kamel
Published: July 2021

Purpose

The current study provides new insights into the relationships between knowledge development (KD) and sustainable supply chain performance (SSCP) by exploring the mediating effects of entrepreneurial orientation (EO) in terms of innovativeness, proactiveness and risk taking.

Design/methodology/approach

Data were collected by questionnaire survey from 242 manufacturing organizations. Structural equation modeling (SEM) was used to test the hypotheses.

Findings

The results reveal that innovativeness and proactiveness have full mediating effects on the relationship between KD and SSCP. Though KD is negatively related to risk taking and has insignificant indirect effect on SSCP via risk taking, the mediating effect of risk taking remains moderate positive on the relationship between KD and SSCP.

Research limitations/implications

Given that the current study focuses on manufacturing sector, future research is needed for more comparative studies conducted in different sectors and cultural contexts. The negative link between KD and risk taking also warrants future investigation.

Practical implications

Organizations may reduce their level of risk taking due to the increase in KD. However, in order to enhance SSCP, risk taking is still needed as it mediates the relationship between KD and SSCP.

Originality/value

The mediating effects of innovativeness, proactiveness and risk taking on the relationship between KD and SSCP are unknown. Current study aims to address this gap.
Inferences on enacted understanding: using immersive technologies to assess intuitive physical science knowledge
Authors: Tscholl Michael , Morphew Jason , Lindgren Robb
Published: July 2021

Purpose

This study aims to advance the proposal to use immersive virtual learning environments to stimulate and reveal deep-seated knowledge about science, giving instructors and researchers unique possibilities for assessing and identifying intuitive physical science knowledge. Aside from the ability to present rich and dynamic stimuli, these environments afford bodily enactment of people’s understanding, which draws less from declarative knowledge stores and more from everyday experiences with the physical world.

Design/methodology/approach

The authors ground their proposal in a critical review of the impact of stimulus and task characteristics of traditional physics inventories. Using a grounded theory approach, the authors present classifications and interpretations of observed bodily enactments of physics understandings in a study where participants enacted their understanding of force and motion of space in an immersive, interactive mixed reality (MR) environment.

Findings

The authors find that instances of these action categories can be interpreted as relating to underlying knowledge, often identified by other studies. The authors thus replicate a number of prior findings, which provide evidence to establish validation for using MR simulation as a tool for identifying people’s physical intuitions.

Research limitations/implications

This study targeted only a few specific physical science scenarios. Further, while a number of key insights about student knowledge came from the analysis, many of the observations are mere leads in need of further investigation and interpretation rather than core findings.

Originality/value

Immersive digital learning environments are primarily used for instruction. The authors propose to use and design them for assessment as well. This paper should prompt more research and development in this direction.
When to choose market foreclosure and vertical mergers with substitutable final products
Authors: Zhang Huailiang , Zhou Yan , Jiang Minghui
Published: July 2021

Purpose

Based on the idea of part standardisation and product differentiation in lean management, this paper answers the question when integrate firms should choose market foreclosure to maximise profits by studying a two-tier supply chain, which contains three types of firms: suppliers, manufacturers and integrated firms. Moreover, the effect of the substitutability between final products and the competition among firms in the supply chain would be investigated from the perspective of dynamic analysis.

Design/methodology/approach

Considering the decision order of integrated firms and manufacturers in the downstream of the supply chain, the authors build three competition models. In each model, integrated firms compete with manufacturers in Bertrand–Nash fashion. And, suppliers compete with each other in Cournot fashion, so do integrated firms and manufacturers. The authors further discuss how the competitive relationship between firms affect the equilibrium result.

Findings

Numerical analysis reveals that under other conditions unchanged, the increased competition between downstream firms leads to the rise in the willingness of selling parts for integrated firms, while the increase in the number of suppliers has the opposite effect. In addition, due to the market change before and after the vertical merger, it may lead to the transition from profitable to unprofitable for the vertical merger.

Originality/value

This paper provides a theoretical analysis and managerial implication for integrated firms' market foreclosure decision. From the perspective of dynamic analysis, this paper demonstrates the result of vertical mergers and provides an explanation for the failure of vertical mergers.
The demoralization of society and the proliferation of organization
Authors: Rachlitz Kurt , Grossmann-Hensel Benjamin , Friedl Ronja
Published: July 2021

Purpose

In this paper, the authors aim to clarify the relationship between organization and society. They argue that the proliferation of organization in modernity has not yet been properly understood in light of the absence of organization in premodern times. The authors therefore ask: Why do organizations proliferate? Why do they proliferate in such manifold organizational forms? And how can these heterogeneous forms nevertheless be related to a common problem to which organizations provide a solution? A comparative historical analysis based on the theory of social systems reveals that organizations fill a gap which the decline of morality as an integrative success medium created.

Design/methodology/approach

The paper develops a conceptual framework focusing on the theory of media within Luhmann’s theory of social systems as a point of departure. The authors discuss the concept of “interpenetration” to assess the relation between morality and organization. They raise several follow-up questions for future empirical research, most prominently pertaining to the relationship between organization and digitalization.

Findings

The main finding is that morality can be conceptualized as a specific success medium (alongside religion and symbolically generalized communication media) which used to structure premodern societies by means of social and interhuman interpenetration at once. Modern society instead employs two differentiated forms of interpenetration: Social interpretation through organizations and interhuman interpenetration through love relationships. These centripetal counterforces help to mediate the centrifugal forces unleashed by the full development of modern success media. Modern society critically depends on the proliferation of organizations.

Originality/value

This paper examines the relationship between morality and organization not from the perspective of interaction or organization, but from the perspective of society. This approach provides novel insights in that it opens up promising avenues of comparison between organization and other social forms. Understanding the distinctively modern “success story” of organization as a social form makes it possible to ask about corresponding potentials and limitations, but also alternative possibilities. In doing so, the authors depart from most studies of organizations grounded in social systems theory as the authors primarily focus on Luhmann’s theory of media (as opposed to the theory of differentiation).
Talking inclusion into being: communication as a facilitator and obstructor of an inclusive work environment
Authors: Wolfgruber Daniel , Stürmer Lina , Einwiller Sabine
Published: July 2021

Purpose

The purpose of this article is to examine the communicative factors that facilitate or hamper the development of an inclusive work environment with an emphasis on the communication about equality, diversity, and inclusion (EDI), while taking diversity characteristics of employees into account.

Design/methodology/approach

In total, 84 persons employed in Austria and Germany, who feature various observable and non-observable diversity characteristics, were interviewed following a problem-centered approach.

Findings

The results indicate that employees with (observable) diversity characteristics, who tend to feel less included, observe more excluding and marginalizing communication and practices in their organizations. Moreover, formal interpersonal communication appears to be more important to develop a highly inclusive workplace than informal interpersonal communication and other forms of communication about EDI.

Research limitations/implications

The sample was rather imbalanced and comprised only employees in Austria and Germany, which limits the study's explanatory power. However, the findings stress the significance of formal interpersonal communication as the cornerstone of an inclusive workplace, which should be followed up in future research.

Practical implications

In terms of the development of an inclusive work environment the findings suggest that strategic (i.e. formal) organizational communication about EDI issues is key to increase the perception of inclusion.

Originality/value

This paper contributes to the literature by demonstrating the importance of interpersonal communication as a key factor that facilitates, but also hampers an inclusive work environment.
Innovation mediating relationship between TQM and performance: cases of industrial certified companies
Authors: Khalfallah Meriem , Ben Salem Anis , Zorgati Hajer , Lakhal Lassaad
Published: July 2021

Purpose

The purpose of this research is to analyze the reciprocal relation between total quality management (TQM) and innovation (product innovation and process innovation) and their impact on operational and financial performance.

Design/methodology/approach

The data were obtained from a survey of 205 manufacturing companies. Structural equation modeling (SEM) was performed to evaluate the research model.

Findings

The results reveal that there is a reciprocal relationship between TQM and innovation. Moreover, the findings indicate a significant positive effect of product innovation and process innovation on operational performance and insignificant direct impact of TQM on operational performance. However, this effect is significant when it is mediated through product innovation and process innovation.

Research limitations/implications

This paper helps practitioners to understand how TQM practices support both product and process innovation and the role of the latter in promoting the implementation of TQM practices and ensuring operational performance.

Originality/value

This study presents an innovative approach since it is among the first research studies that provide empirical evidence to a reciprocal association between TQM and innovation. Additionally, this paper examines the dimensions studied in different aspects. It considered financial performance and operational performance, and with respect to innovation, this dimension was analyzed through two different perspectives, namely product innovation and process innovation. This study is also among the first and few research studies that have studied the mediating effect of innovation.
Pyricularia sp. jiangsuensis, a new cryptic rice panicle blast pathogen from rice fields in Jiangsu Province, China
Authors: Du Yan , Qi Zhongqiang , Liang Dong , Yu Junjie , Yu Mina , Zhang Rongsheng , Cao Huijuan , Yong Mingli , Pan Xiayan , Yin Xiaole , Qiao Junqing , Liu Youzhou , Chen Zhiyi , Song Tianqiao , Liu Wende , Zhang Zhengguang , Liu Yongfeng
Published: July 2021

Pyricularia oryzae is a multi‐host pathogen causing cereal disease, including the devastating rice blast. Panicle blast is a serious stage, leading to severe yield loss. Thirty‐one isolates (average 4.1%) were collected from the rice panicle lesions at nine locations covering Jiangsu province from 2010 to 2017. These isolates were characterized as Pyricularia sp. jiangsuensis distinct from known Pyricularia species. The representative strain 18‐2 can infect rice panicle, root and five kinds of grasses. Intriguingly, strain 18‐2 can co‐infect rice leaf with P. oryzae Guy11. The whole genome of P. sp. jiangsuensis 18‐2 was sequenced. Nine effectors were distributed in translocation or inversion region, which may link to the rapid evolution of effectors. Twenty‐one homologues of known blast‐effectors were identified in strain 18‐2, seven effectors including the homologues of SLP1, BAS2, BAS113, CDIP2/3, MoHEG16 and Avr‐Pi54, were upregulated in the sample of inoculated panicle with strain 18‐2 at 24 hpi compared with inoculation at 8 hpi. Our results provide evidences that P. sp. jiangsuensis represents an addition to the mycobiota of blast disease. This study advances our understanding of the pathogenicity of P. sp. jiangsuensis to hosts, which sheds new light on the adaptability in the co‐evolution of pathogen and host.
Beyond Causality: Additional Benefits of Randomized Controlled Trials for Improving Health Care Delivery
Authors: ALSAN MARCELLA , FINKELSTEIN AMY N.
Published: July 2021

Policy Points

Policymakers at federal and state agencies, health systems, payers, and providers need rigorous evidence for strategies to improve health care delivery and population health. This is all the more urgent now, during the COVID‐19 pandemic and its aftermath, especially among low‐income communities and communities of color.

Randomized controlled trials (RCTs) are known for their ability to produce credible causal impact estimates, which is why they are used to evaluate the safety and efficacy of drugs and, increasingly, to evaluate health care delivery and policy. But RCTs provide other benefits, allowing policymakers and researchers to: 1) design studies to answer the question they want to answer, 2) test theory and mechanisms to help enrich understanding beyond the results of a single study, 3) examine potentially subtle, indirect effects of a program or policy, and 4) collaborate closely to generate policy‐relevant findings.

Illustrating each of these points with examples of recent RCTs in health care, we demonstrate how policymakers can utilize RCTs to solve pressing challenges.
Investigation of microbial contamination in a chicken slaughterhouse environment
Authors: Song Xiangyu , Wang Huhu , Xu Xinglian
Published: July 2021

The environment in poultry abattoirs is the primary potential source of bacterial contamination and cross‐contamination of broiler carcasses. In this context, we explored the influence of chilling water and contact surfaces on the microbial diversity of broiler carcasses in warm and cold seasons. High‐throughput sequencing was used to target the V3‐V4 region of the 16S rRNA gene. Proteobacteria was the main phylum detected in broiler carcasses and on contact surfaces, whereas Bacteroidetes and Firmicutes had high abundances of the prechilling water in both seasons. At the genus level, Psychrobacter and Acinetobacter were much more abundant on broiler carcasses in the warm season, while Flavobacterium and Psychrobacter dominated in the cold season. LEfSe analysis showed that the chilling tank was a key location where carcass contamination occurred. Therefore, the risk of carcass contamination can be reduced by improving sanitary conditions during processing, installing longer chilling tanks, or increasing the water exchange rate in chilling tanks. The results of this study may be useful for better slaughterhouse environmental hygiene management in different seasons.

Practical Application

This study will help poultry processing managers better understand the impact of different seasons on the environmental microbiota in the environment and their abundance in poultry processing plants, thus allowing them to adopt proper disinfection strategies for different seasons and environments, further improving the safety and shelf life of products.
Multiple myeloma with t(11;14)‐associated immature phenotype has lower CD38 expression and higher BCL2 dependence
Authors: Kitadate Akihiro , Terao Toshiki , Narita Kentaro , Ikeda Sho , Takahashi Yuto , Tsushima Takafumi , Miura Daisuke , Takeuchi Masami , Takahashi Naoto , Matsue Kosei
Published: July 2021

CD38 expression on myeloma cells is a critical factor affecting the early response to the anti‐CD38 antibody daratumumab. However, factors affecting CD38 expression in untreated multiple myeloma are not fully elucidated. In this study, we found that CD38 expression was significantly lower in myeloma patients with the translocation t(11;14)‐associated immature plasma cell phenotype, and particularly in those expressing B–cell‐associated genes such as PAX5 and CD79A. CD138, a representative marker of plasmacytic differentiation, was also significantly lower in these patients, suggesting that CD38 expression may be associated with the differentiation and maturation stages of myeloma cells. Furthermore, the BCL2/BCL2L1 ratio, a response marker of the BCL2 inhibitor venetoclax, was significantly higher in patients with the immature phenotype expressing B–cell‐associated genes. The BCL2/BCL2L1 ratio and CD38 expression were significantly negatively correlated. We also confirmed that patients with translocation t(11;14) expressing B–cell‐associated genes were indeed less sensitive to daratumumab‐mediated direct cytotoxicity but highly sensitive to venetoclax treatment in ex vivo assays. Moreover, all‐trans‐retinoic acid, which enhances CD38 expression and induces cell differentiation in myeloma cells, reduced B‐cell marker expression and the BCL2/BCL2L1 ratio in myeloma cell lines, leading to reduced efficacy of venetoclax. Venetoclax specifically induces cell death in myeloma with t(11;14), although why patients with translocation t(11;14) show BCL2 dependence is unclear. These results suggest that BCL2 dependence, as well as CD38 expression, are deeply associated with the differentiation and maturation stages of myeloma cells. This study highlights the importance of examining t(11;14) and considering cell maturity in myeloma treatment strategies.
The impact of ageing and menopause in women with polycystic ovary syndrome
Authors: Helvaci Nafiye , Yildiz Bulent O.
Published: July 2021

Polycystic ovary syndrome (PCOS) is a common hormonal, metabolic and reproductive disorder. Women with PCOS at reproductive age have increased risk and prevalence of prediabetes and diabetes and have multiple risk factors for cardiometabolic disease and other comorbidities such as obstructive sleep apnoea, endometrial cancer and mood disorders, which contribute to the overall health burden of the syndrome. However, little is known about the impact of PCOS on long‐term health in ageing women. In this review, we aimed to give an updated overview regarding the long‐term health outcomes of PCOS and their clinical implications in peri‐ and postmenopause. The PCOS phenotype ameliorates with ageing and limited available data suggest that there is no further deterioration in cardiometabolic profile in women with PCOS after menopause. Accordingly, the risk of cardiovascular disease in ageing women with PCOS seems to be no different from those without PCOS and lower than previously anticipated based on their risk during reproductive years. Regarding other comorbidities including sleep apnoea, mood disorders and endometrial cancer, it is difficult to determine the true risk in older women with PCOS due to the confounding factors and lack of long‐term cohort studies. Large, prospective studies on community‐based and well‐phenotyped PCOS cohorts with extended follow‐up into late menopause are needed to confirm these findings.
Comparison of the accuracy of implant placement using different drilling systems for static computer‐assisted implant surgery: A simulation‐based experimental study
Authors: Sittikornpaiboon Paknisa , Arunjaroensuk Sirida , Kaboosaya Boosana , Subbalekha Keskanya , Mattheos Nikos , Pimkhaokham Atiphan
Published: July 2021

Background

Different designs of surgical drilling systems have been developed for the purpose of static Computer‐Assisted Implant Surgery (sCAIS), but there is at present little understanding of how design principles affect the accuracy of implant placement.

Purpose

The aim of this in vitro study was to compare the accuracy of implant placement among five drilling systems of sCAIS in a controlled experimental setting.

Materials and Methods

Twenty‐five 3D printed models with two edentulous bilateral premolar spaces were allocated to five different drilling systems: group A: sleeve‐in‐sleeve, group B: sleeve‐in‐sleeve with self‐locking, group C: mounted sleeve‐on‐drill, group D: integrated sleeve‐on‐drill with metal sleeve in the guide, group E: integrated sleeve‐on‐drill without metal sleeve. Models were scanned with CBCT and optical scanner. All implants were digitally planned and 10 implants placed with sCAIS in each group. Postoperative 3D deviation of placed vs planned position was measured by means of platform, apex and angular deviation. Data was analyzed using Kruskal‐Wallis test (P ≤ .05). Pairwise comparisons were tested with Dunn's test with adjusted P values.

Results

The overall platform deviation ranged from 0.42 ± 0.12 mm (group B) to 1.18 ± 0.19 mm (group C). The overall apex deviation ranged from 0.76 ± 0.22 mm (group B) to 1.95 ± 0.48 mm (group D). The overall angular deviation ranged from 2.50 ± 0.89 degree (group B) to 5.30 ± 1.04 degree (group E). Group A and B showed significantly less angular deviation than groups D and E (P < .05). There was no statistically significant differences in all parameters between group A and B, as well as between group D and E (P > .05).

Conclusions

Significant differences were found with regards to accuracy among the five sCAIS systems tested, suggesting that the drilling protocol, the devices used and the design principles of the guides could influence the accuracy of implant placement.
Global change on the roof of the world: Vulnerability of Himalayan otter species to land use and climate alterations
Authors: Jamwal Pushpinder S. , Di Febbraro Mirko , Carranza Maria Laura , Savage Melissa , Loy Anna
Published: July 2021

Aim

Climate Change Vulnerability Assessment (CCVA) prescribes the quantification of species vulnerability based on three components: sensitivity, adaptive capacity and exposure. Such assessments should be performed through combined approaches that integrate trait‐based elements (e.g., measures of species sensitivity such as niche width) with correlative tools quantifying exposure (magnitude of changes in climate within species habitat). Furthermore, as land use alterations may increase climate impacts on biodiversity, CCVAs should focus on both climate and land use change effects. Unfortunately, most of such assessments have so far focused exclusively on exposure to climate change.

Location

Himalaya.

Methods

We evaluated the vulnerability of three otter species occurring in the Himalayan region, that is, Aonyx cinereus, Lutra lutra and Lutrogale perspicillata, to 2050 climate and land use change through the recently proposed Climate Niche Factor Analysis (CNFA) framework combined with Species Distribution Models.

Results

Future climate and land use change will reduce (6%–15%) and shift (10%–18%) the geographical range of the three species in the Himalaya, with land use alterations exerting far more severe effects than climate change. Among vulnerability components, sensitivity played a greater role than exposure in determining the vulnerability of the otters. Specifically, the most specialist species, L. perspicillata, showed the highest vulnerability in comparison with the most generalist, L. lutra.

Main conclusions

Our results underline how coupling climate and land use change components in CCVAs can generate diverging predictions of species vulnerability compared to approaches relying on climate change only. Moreover, intrinsic components, such as species sensitivity, proved significantly more important in determining vulnerability than extrinsic metrics such as habitat exposure.
The thermal ecology of burying beetles: temperature influences reproduction and daily activity in Nicrophorus marginatus
Authors: Keller Maranda L. , Howard Daniel R. , Hall Carrie L.
Published: July 2021

1. Understanding how organisms respond to thermal stress can help predict long‐term population viability under projected climate change models. Behavioural plasticity can mediate the impact of thermal stress; however, some behavioural modifications in response to novel environments act maladaptively and could implicate population persistence.

2. Burying beetles (Silphidae: Nicrophorus) have been found to modify traits related to individual fitness to be favourable in their perceived environments. To reproduce, breeding individuals of the nicrophorine genus work together to bury and prepare a suitable vertebrate carcass as food for their developing larvae.

3. Here, we explore how sustained temperature treatments influence traits that closely tie to individual fitness in Nicrophorus marginatus. We measure carcass handling, reproductive output, and activity levels in controlled and elevated temperature treatments.

4. At only 27.5 °C, we observed significantly reduced reproductive success rates, extended carcass handling time, and increased levels of activity when compared to the baseline temperature treatment of 26 °C. Additionally, at 26.5 °C, we document reduced brood size.

5. These findings indicate that slight incremental increases in temperature could have profound effects on burying beetle fitness when experienced for extended periods.
The role of long noncoding RNA THAP9‐AS1 in the osteogenic differentiation of dental pulp stem cells via the miR‐652‐3p/VEGFA axis
Authors: Wang Jia , Liu Xueyu , Wang Yue , Xin Bingchang , Wang Wei
Published: July 2021

Dental pulp stem cells (DPSCs) are multipotent and may play crucial roles in dentin‐pulp regeneration. Recent studies have revealed that long noncoding RNAs (lncRNAs) are implicated in the osteogenic differentiation of DPSCs. However, the specific role and potential mechanisms of the lncRNA trihydroxyacetophenone domain containing nine antisense RNA 1 (THAP9‐AS1) during osteogenic differentiation of DPSCs remain unknown. In the present study, we determined that THAP9‐AS1 expression was upregulated during osteogenic differentiation of DPSCs. Moreover, we investigated the biological functions of THAP9‐AS1 during osteogenic differentiation of DPSCs by loss‐of‐function assays. THAP9‐AS1 knockdown inhibited osteogenic differentiation of DPSCs by decreasing alkaline phosphatase activity, alkaline phosphatase‐positive cell ratio, mineralizing matrix and mRNA, and protein levels of early osteogenic‐markers. We also found that THAP9‐AS1 interacted with miR‐652‐3p, whose downstream gene target is vascular endothelial growth factor A (VEGFA). In addition, rescue assays indicated that VEGFA rescued the effects of THAP9‐AS1 knockdown during osteogenic differentiation of DPSCs. In summary, we verified that knockdown of THAP9‐AS1 inhibits osteogenic differentiation of DPSCs via the miR‐652‐3p/VEGFA axis. Our findings may be helpful to extend research on the mechanisms underlying osteogenic differentiation of DPSCs.
Long‐term safety and efficacy of add‐on cannabidiol in patients with Lennox–Gastaut syndrome: Results of a long‐term open‐label extension trial
Authors: Patel Anup D. , Mazurkiewicz‐Bełdzińska Maria , Chin Richard F. , Gil‐Nagel Antonio , Gunning Boudewijn , Halford Jonathan J. , Mitchell Wendy , Scott Perry Michael , Thiele Elizabeth A. , Weinstock Arie , Dunayevich Eduardo , Checketts Daniel , Devinsky Orrin
Published: July 2021

Objective

Lennox–Gastaut syndrome (LGS) is an epileptic encephalopathy that is often treatment resistant. Efficacy and safety of add‐on cannabidiol (CBD) to treat seizures associated with LGS was demonstrated in two randomized controlled trials (RCTs). Patients who completed the RCTs were invited to enroll in this long‐term open‐label extension (OLE) trial, GWPCARE5 (NCT02224573). We present the final analysis of safety and efficacy outcomes from GWPCARE5.

Methods

Patients received plant‐derived highly purified CBD (Epidiolex in the United States; Epidyolex in the European Union; 100 mg/ml oral solution), titrated to a target maintenance dose of 20 mg/kg/day over 2 weeks. Based on response and tolerability, CBD could then be reduced or increased up to 30 mg/kg/day.

Results

Of 368 patients with LGS who completed the RCTs, 366 (99.5%) enrolled in this OLE. Median and mean treatment duration were 1090 and 826 days (range = 3–1421), respectively, with a mean modal dose of 24 mg/kg/day. Adverse events (AEs) occurred in 96% of patients, serious AEs in 42%, and AE‐related discontinuations in 12%. Common AEs were convulsion (39%), diarrhea (38%), pyrexia (34%), and somnolence (29%). Fifty‐five (15%) patients experienced liver transaminase elevations more than three times the upper limit of normal; 40 (73%) were taking concomitant valproic acid. Median percent reductions from baseline ranged 48%–71% for drop seizures and 48%–68% for total seizures through 156 weeks. Across all 12‐week visit windows, 87% or more of patients/caregivers reported improvement in the patient's overall condition on the Subject/Caregiver Global Impression of Change scale.

Significance

Long‐term add‐on CBD treatment had a similar safety profile as in the original RCTs. Sustained reductions in drop and total seizure frequency were observed for up to 156 weeks, demonstrating long‐term benefits of CBD treatment for patients with LGS.