bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinically relevant mutations of mycobacterial GatCAB inform regulation of translational fidelity
Authors: Li Yang-Yang , Cai Rong-Jun , Yang Jia-Ying , Hendrickson Tamara L. , Xiang Ye , Javid Babak
Published: March 2021

Most bacteria employ a two-step indirect tRNA aminoacylation pathway for the synthesis of aminoacylated tRNAGlnand tRNAAsn. The heterotrimeric enzyme GatCAB performs a critical amidotransferase reaction in the second step of this pathway. We have previously demonstrated in mycobacteria that this two-step pathway is error-prone and translational errors contribute to adaptive phenotypes such as antibiotic tolerance. Furthermore, we identified clinical isolates of the globally important pathogenMycobacterium tuberculosiswith partial loss-of-function mutations ingatA, and demonstrated that these mutations result in high, specific rates of translational error and increased rifampicin tolerance. However, the mechanisms by which these clinically-derived mutations ingatAimpact GatCAB function was unknown. Here, we describe biochemical and biophysical characterization ofM. tuberculosisGatCAB, containing either wild-typegatAor one of twogatAmutants from clinical strains. We show that these mutations have minimal impact on enzymatic activity of GatCAB; however, they result in destabilization of the GatCAB complex as well as that of the ternary asparaginyl-transamidosome. Stabilizing complex formation with the solute trehalose increases specific translational fidelity of not only the mutant strains, but also of wild-type mycobacteria. Therefore, our data suggest that alteration of GatCAB stability may be a mechanism for modulation of translational fidelity.
Atg39 links and deforms the outer and inner nuclear membranes in selective autophagy of the nucleus
Authors: Mochida Keisuke , Otani Toshifumi , Katsumata Yuto , Kirisako Hiromi , Kakuta Chika , Kotani Tetsuya , Nakatogawa Hitoshi
Published: March 2021

In selective autophagy of the nucleus (hereafter nucleophagy), nucleus-derived double membrane vesicles (NDVs) are formed, sequestered within autophagosomes, and delivered to lysosomes or vacuoles for degradation. In Saccharomyces cerevisiae, the nuclear envelope (NE) protein Atg39 acts as a nucleophagy receptor, which interacts with Atg8 to target NDVs to forming autophagosomal membranes. In this study, we revealed that Atg39 is anchored to the outer nuclear membrane (ONM) via its transmembrane domain and also associated with the inner nuclear membrane (INM) via membrane-binding amphipathic helices (APHs) in its perinuclear space region, thereby linking these membranes. We also revealed that overaccumulation of Atg39 causes the NE to protrude towards the cytoplasm, and the tips of the protrusions are pinched off to generate NDVs. The APHs of Atg39 are crucial for Atg39 assembly in the NE and subsequent NE protrusion. These findings suggest that the nucleophagy receptor Atg39 plays pivotal roles in NE deformation during the generation of NDVs to be degraded by nucleophagy.
Non-parallel morphological divergence following colonization of a new host plant
Authors: Nilsson Kalle J. , Ortega Jesús , Friberg Magne , Runemark Anna
Published: March 2021

Divergent ecological selection may diversify conspecific populations evolving into different niches, and may lead to speciation if gene flow is ceased, e.g, due to reinforcement leading to character displacement. Adaptation to the same niche is expected to be parallel. Whether selection against maladaptive hybridization in secondary sympatry also results in parallel divergence in traits that are not directly related to the ecological niches remains an empirical challenge, although such character displacement can be decisive for if ecotypes develop into new species. Here, we use a host shift in the phytophagous peacock flyTephritis conura, with both host races represented in two geographically separate areas East and West of the Baltic Sea to investigate convergence in morphological adaptations. We asked i) if there are consistent morphological adaptations to a host plant shift and ii) if the response to secondary sympatry with the alternate host race is parallel across contact zones. We found surprisingly low and variable, albeit significant, divergence between host races. Only one trait, the length of the female ovipositor, which serves an important function in the interaction with the hosts, was consistently different. Instead, co-existence with the other host race significantly affected the degree of morphological divergence, but the divergence was largely driven by different traits in different contact zones. Thus, local stochastic fixation or reinforcement could generate trait divergence, and additional evidence is needed to conclude whether divergence is locally adaptive.
TheC. elegansPTCHD homolog PTR-4 is required for proper organization of the pre-cuticular apical extracellular matrix
Authors: Cohen Jennifer D. , del Castillo Carla E. Cadena , Kaech Andres , Spang Anne , Sundaram Meera
Published: March 2021

The Patched-related (PTR) superfamily of transmembrane proteins can transport lipids or other hydrophobic molecules across cell membranes. While the hedgehog receptor Patched has been intensively studied, much less is known about the biological roles of other PTR or Patched domain (PTCHD) family members.C. eleganshas a large number of PTR/PTCHD proteins, despite lacking a canonical hedgehog pathway. Here, we show that PTR-4 promotes the assembly of the pre-cuticle apical extracellular matrix (aECM), a transient and molecularly distinct aECM that precedes and patterns the later collagenous cuticle or exoskeleton.ptr-4mutants share many phenotypes with pre-cuticle mutants, including defects in eggshell dissolution, tube shaping, alae (cuticle ridge) structure, and cuticle barrier function. PTR-4 localizes to the apical side of a subset of outward-facing epithelia, in a cyclical manner that peaks when pre-cuticle matrix is present. Finally, PTR-4 acts in a cell non-autonomous manner to properly localize the secreted ZP domain protein LET-653 to the pre-cuticle aECM. We propose that PTR-4 exports lipids or other hydrophobic components of the pre-cuticle aECM.
In vitroteratogenicity testing using a 3D, embryo-like gastruloid system
Authors: Mantziou Veronika , Baillie-Benson Peter , Jaklin Manuela , Kustermann Stefan , Arias Alfonso Martinez , Moris Naomi
Published: March 2021

Pharmaceuticals that are intended for use in patients of childbearing potential need to be tested for teratogenicity before marketing. Several pharmaceutical companies use animal-freein vitromodels which allow a more rapid selection of lead compounds and contribute to 3Rs principles (‘replace, reduce and refine’) by streamlining the selection of promising compounds that are submitted to further regulatory studies in animals. Currently availablein vitromodels typically rely on adherent monolayer cultures or disorganized 3D structures, both of which lack the spatiotemporal and morphological context of the developing embryo. A newly developed 3D ‘gastruloid’ model has the potential to achieve a more reliable prediction of teratogenicity by providing a robust recapitulation of gastrulation-like events alongside morphological coordination at relatively high-throughput. In this first proof-of-concept study, we used both mouse and human gastruloids to examine a panel of seven reference compounds, with associatedin vivodata and known teratogenic risk, to quantitatively assessin vitroteratogenicity. We observed several gross morphological effects, including significantly reduced elongation or decreased size of the gastruloids, upon exposure to several of the reference compounds. We also observed aberrant gene expression using fluorescent reporters, includingSOX2, BRA, andSOX17, suggestive of multi-lineage differentiation defects and disrupted axial patterning. Finally, we saw that gastruloids recapitulated some of the knownin vivospecies-specific susceptibilities between their mouse and human counterparts. We therefore suggest that gastruloids represent a powerful tool for teratogenicity assessment by enabling relevant physiological recapitulation of early embryonic development, demonstrating their use as a novelin vitroteratogenic model system.
Crystal structures of β-1,4-N-acetylglucosaminyltransferase 2: structural basis for inherited muscular dystrophies
Authors: Yang Jeong Yeh , Halmo Stephanie M. , Praissman Jeremy , Chapla Digantkumar , Singh Danish , Wells Lance , Moremen Kelley W. , Lanzilotta William N.
Published: March 2021

The canonical O-mannosylation pathway in humans is essential for the functional glycosylation of α-dystroglycan. Disruption of this post-translational modification pathway leads to congenital muscular dystrophies. The first committed step in the construction of a functional matriglycan structure involves the post-translational modification of α-dystroglycan. This is essential for binding extracellular matrix proteins and arenaviruses, and is catalyzed by β-1,4-N-acetylglucosaminyltransferase 2 (POMGNT2). While another glycosyl transferase, β-1,4-N-acetylglucosaminyltransferase 1 (POMGNT1), has been shown to be promiscuous in extending O-mannosylated sites, POMGNT2 has been shown to display significant primary amino-acid selectivity near the site of O-mannosylation. Moreover, several single point mutations in POMGNT2 have been identified in patients with assorted dystroglycanopathies such as Walker–Warburg syndrome and limb girdle muscular dystrophy. To gain insight into POMGNT2 function in humans, the enzyme was expressed as a soluble, secreted fusion protein by transient infection of HEK293 suspension cultures. Here, crystal structures of POMGNT2 (amino-acid residues 25–580) with and without UDP bound are reported. Consistent with a novel fold and a unique domain organization, no molecular-replacement model was available and phases were obtained through crystallization of a selenomethionine variant of the enzyme in the same space group. Tetragonal (space group P4212; unit-cell parameters a = b = 129.8, c = 81.6 Å, α = γ = β = 90°) crystals with UDP bound diffracted to 1.98 Å resolution and contained a single monomer in the asymmetric unit. Orthorhombic (space group P212121; unit-cell parameters a = 142.3, b = 153.9, c = 187.4 Å, α = γ = β = 90°) crystals were also obtained; they diffracted to 2.57 Å resolution and contained four monomers with differential glycosylation patterns and conformations. These structures provide the first rational basis for an explanation of the loss-of-function mutations and offer significant insights into the mechanics of this important human enzyme.
Protein identification from electron cryomicroscopy maps by automated model building and side-chain matching
Authors: Terwilliger Thomas C. , Sobolev Oleg V. , Afonine Pavel V. , Adams Paul D. , Ho Chi-Min , Li Xiaorun , Zhou Z. Hong
Published: March 2021

Using single-particle electron cryo-microscopy (cryo-EM), it is possible to obtain multiple reconstructions showing the 3D structures of proteins imaged as a mixture. Here, it is shown that automatic map interpretation based on such reconstructions can be used to create atomic models of proteins as well as to match the proteins to the correct sequences and thereby to identify them. This procedure was tested using two proteins previously identified from a mixture at resolutions of 3.2 Å, as well as using 91 deposited maps with resolutions between 2 and 4.5 Å. The approach is found to be highly effective for maps obtained at resolutions of 3.5 Å and better, and to have some utility at resolutions as low as 4 Å.
Using VIKOR with structural equation modeling for constructing benchmarks in the Internet industry
Authors: Torlak Nuri Gökhan , Demir Ahmet , Budur Taylan
Published: March 2021

Purpose

The study uses VIseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR)-structural equation modeling (SEM) to construct benchmarks for service providers and evaluate a multimethodology practice in the Internet industry.

Design/methodology/approach

The data were collected using a survey based on an email/interview with 444 Internet users participating. SEM obtained coefficient values by way of customer expectations for Internet service providers. The authors normalized coefficients and integrated them into the VIKOR method for ranking competitors in the Internet industry.

Findings

VIKOR-SEM revealed that network and information quality and security/privacy significantly positively impact customer trust while network and information quality and customer trust significantly positively affect Internet users' value perceptions. Customer services do not affect customer trust, while security/privacy and customer services have no significant influence on customer value perceptions. Though customer services and Internet users' trust and value perceptions directly, significantly and positively affect their commitments, the quality of network and information and security/privacy indirectly, significantly and positively influence customer commitments.

Research limitations/implications

The study was in the Internet industry of Iraq. The results cannot be accurate for the other countries and the service sectors. The researchers/managers can adopt the model in other service sectors to test the multimethodology.

Originality/value

VIKOR-SEM evaluated the changes in customer expectations and service providers in the Internet industry.
An intelligent simulation-based framework for automated planning of concrete construction works
Authors: Mohammadi Sina , Tavakolan Mehdi , Zahraie Banafsheh
Published: March 2021

Purpose

This paper proposes an innovative intelligent simulation-based construction planning framework that introduces a new approach to simulation-based construction planning.

Design/methodology/approach

In this approach, the authors developed an ontological inference engine as an integrated part of a constraint-based simulation system that configures the construction processes, defines activities and manages resources considering a variety of requirements and constraints during the simulation. It allows for the incorporation of the latest project information and a deep level of construction planning knowledge in the planning. The construction planning knowledge is represented by an ontology and several semantic rules. Also, the proposed framework uses the project building information model (BIM) to extract information regarding the construction product and the relations between elements. The extracted information is then converted to an ontological format to be useable by the framework.

Findings

The authors implemented the framework in a case study project and tested its usefulness and capabilities. It successfully generated the construction processes, activities and required resources based on the construction product, available resources and the planning rules. It also allowed for a variety of analyses regarding different construction strategies and resource planning. Moreover, 4D BIM models that provide a very good understanding of the construction plan can be automatically generated using the proposed framework.

Originality/value

The active integration between BIM, discrete-event simulation (DES) and ontological knowledge base and inference engine defines a new class of construction simulation with expandable applications.
Audit quality implications of regulatory change in South Africa
Authors: Ndaba Harina , Harber Michael , Maroun Warren
Published: March 2021

Purpose

This paper explores how technical constructions of audit practice are influenced by mandatory audit firm rotation (MAFR) regulations. The paper responds to calls for additional research on how external regulation influences audit quality and supplements the predominately quantitative research dealing specifically with firm rotation and its relevance for audit quality.

Design/methodology/approach

Data are collected from South Africa which is the latest jurisdiction to adopt MAFR (from 2017). Detailed interviews with 49 participants comprising 24 audit partners and 25 non-auditors are conducted to explore how MAFR can impact audit quality. For this purpose, audit quality is defined according to a schematic developed interpretively and based on professional auditing standards and the prior research on audit quality.

Findings

There is no guarantee that MAFR will bolster auditors' independence or contribute to a more thorough audit approach. On the contrary, the effort required by incoming audit firms to gain an understanding of new clients coupled with material tendering costs is expected to decrease the profitability of audit engagements with adverse implications for audit quality. A loss of client experience and staff retention challenges may contribute further to a decline in audit quality. There may be some improvements to audit practice when an incumbent firm's work is going to be scrutinised by a new auditor but audit methodologies, including the nature and extent of testing performed, are not expected to change significantly because of MAFR. In this way, the regulation may be a symbolic response to a perceived decline in audit quality and auditor independence rather than part of an effective strategy to encourage more rigorous audit practice for the benefit of the users of financial statements.

Originality/value

The current paper provides one of the first exploratory accountants of how MAFR is expected to impact audit practice and, in turn, audit quality. The research responds to the call for more field-work studies on the mechanics of the audit process by engaging directly with practitioners instead of relying on inferential testing of broad audit quality surrogates. The study also makes an important empirical contribution by providing primary evidence on how external regulation influences audit practice from a seldom studied African perspective.
Determinants of working capital: empirical evidence on manufacturing SMEs
Authors: Sardo Filipe , Serrasqueiro Zélia
Published: March 2021

Purpose

This study seeks to analyse the determinants of working capital of manufacturing small and medium-sized enterprises (SMEs), particularly the effect of the probability of financial distress on working capital.

Design/methodology/approach

Using panel data models, the authors analyse a sample of 3994 manufacturing SMEs for the period 2011–2017.

Findings

The results suggest that SMEs pursue conservative working capital management to avoid the failure to fulfil the commitments with creditors. Also, the positive impact of the probability of financial distress on SME working capital suggests that SMEs exposed to a higher probability of bankruptcy invest more in working capital to avoid the risk of default and financing imbalance.

Originality/value

The novelty of this study is to extend the consequences of aggressive or conservative working capital management by analysing the probability of financial distress on working capital.
E-store brand personality congruence for multichannel apparel retail brands
Authors: Chang Jae Youn , Kwon Wi-Suk
Published: March 2021

Purpose

This study aims at examining the role of the e-store brand personality congruence/incongruence of a multichannel apparel retailer in the formation of consumers' perceived e-store brand fit and e-store patronage intention, based on the concept of image congruence.

Design/methodology/approach

An online survey was conducted with a US national sample of 458 female consumers (20–50 years old) who had shopped for clothing online.

Findings

Results revealed that e-store brand personality incongruence in three personality dimensions had a negative impact on consumers' e-store patronage intention directly as well as indirectly by reducing the consumers' global perception of the e-store brand fit. Further, the retailer's relevance to the consumer moderated the relationship between the perceived e-store brand fit and e-store patronage intention in that this relationship was significantly greater among consumers with a high (vs low) perceived self-relevance of the retail brand.

Practical implications

The findings highlight the importance of symbolically integrated cross-channel brand management for multichannel apparel retailers by clearly identifying their brand personality and carefully crafting it into their e-store interface design and e-store visual merchandising to convey the brand personality.

Originality/value

This study expands the application of image congruence to the cross-channel image congruence phenomenon in multichannel retailing environments by examining the e-store brand image congruence employing both direct and indirect approaches.
Managing funerary systems in the pandemic: lessons learned and an application of a scenario simulation in São Paulo City, Brazil
Authors: de Brito Jr Irineu , Cunha Manoel Henrique Capistrano , Tozi Luiz Antonio , Franzese Luiz Augusto , Frazão Márcia Lorena da Silva , Bressane Adriano
Published: March 2021

Purpose

This study, a practice forum article, aims to presents the lessons learned and the development of a discrete event simulation model to support the funerary system management of São Paulo City, Brazil, during the COVID-19 pandemic.

Design/methodology/approach

A discrete event simulation model was developed by the authors as soon as the pandemic affected the city of São Paulo, Brazil. Based on the model, several scenarios with varying minimum, median and peak demands (i.e. the number of deaths) were tested and evaluated. The lessons learned from the scenario analysis and implementation of the decision-making of the city government of São Paulo are discussed in this article.

Findings

The lessons learned about the coordination, inventory management and other operational characteristics in funerary logistics during the pandemic are shared with a model, which quantifies the demand for vehicles, coffins, graves and teams in the cemeteries in different simulated scenarios.

Practical implications

The São Paulo State Civil Defense used this information during the pandemic to prepare the funerary system of the municipality.

Social implications

The study presents methods to mitigate the sanitary, environmental and psychosocial problems related to the funerary system.

Originality/value

Studies on funerary systems are scarce. This study presents the results that supported the dimensioning of the funerary system during the pandemic and operational lessons about the logistics to support decision-making in future events.
Making a difference: workforce skills and capacity for integrated care
Authors: Akehurst Joy , Stronge Paul , Giles Karen , Ling Jonathon
Published: March 2021

Purpose

The aim of this action research was to explore, from a workforce and a patient/carer perspective, the skills and the capacity required to deliver integrated care and to inform future workforce development and planning in a new integrated care system in England.

Design/methodology/approach

Semi-structured interviews and focus groups with primary, community, acute care, social care and voluntary care, frontline and managerial staff and with patients and carers receiving these services were undertaken. Data were explored using framework analysis.

Findings

Analysis revealed three overarching themes: achieving teamwork and integration, managing demands on capacity and capability and delivering holistic and user-centred care. An organisational development (OD) process was developed as part of the action research process to facilitate the large-scale workforce changes taking place.

Research limitations/implications

This study did not consider workforce development and planning challenges for nursing and care staff in residential, nursing care homes or domiciliary services. This part of the workforce is integral to the care pathways for many patients, and in line with the current emerging national focus on this sector, these groups require further examination. Further, data explore service users' and carers' perspectives on workforce skills. It proved challenging to recruit patient and carer respondents for the research due to the nature of their illnesses.

Practical implications

Many of the required skills already existed within the workforce. The OD process facilitated collaborative learning to enhance skills; however, workforce planning across a whole system has challenges in relation to data gathering and management. Ensuring a focus on workforce development and planning is an important part of integrated care development.

Social implications

This study has implications for social and voluntary sector organisations in respect of inter-agency working practices, as well as the identification of workforce development needs and potential for informing subsequent cross-sector workforce planning arrangements and communication.

Originality/value

This paper helps to identify the issues and benefits of implementing person-centred, integrated teamworking and the implications for workforce planning and OD approaches.
Protecting organizational competitiveness from the hazards of knowledge leakage through HRM
Authors: Fawad Sharif Sayed Muhammad , Yang Naiding , Rehman Atiq ur , Kanwal Fouzia , WangDu Fangmei
Published: March 2021

Purpose

Collaborative projects are useful tools for learning and innovation. However, there is an associated cost – knowledge leakage, which is theoretically linked to challenging organizational competitiveness. The purpose of this study is to examine whether knowledge-oriented human resource (HR) management practices can protect organizations from the adverse effect of knowledge leakage while investigating the moderating role of knowledge-oriented HR management practices.

Design/methodology/approach

This study uses mixed methods involving collection of qualitative data through 13 qualitative interviews and quantitative data through 398 survey questionnaires. SPSS 23 and Process Macro 3.1 have been applied to test the hypotheses.

Findings

The study finds that knowledge leakage adversely affects organizational competitiveness, whereas the effect of knowledge-oriented HR management practices on organizational competitiveness is positive. Further, knowledge-oriented HR practices negatively and significantly moderate the relationship between knowledge leakage and organizational competitiveness. As the strength of the moderator increases, the effect of knowledge leakage tends to diminish. Besides, demographic factors (age of the firm and industry type) do not influence the organizational competitiveness.

Research limitations/implications

This study has several theoretical contributions; first, it contributes to knowledge-based view by empirically establishing the adverse effect of knowledge leakage on organizational competitiveness. Second, knowledge-oriented HR management practices increase organizational competitiveness, which is contribution to HR management literature. Lastly, knowledge-oriented HR management practices protect organizational competitiveness from the adversaries of knowledge leakage, which is contribution to strategic management literature.

Practical implications

Practitioners must invest in knowledge-oriented HR management practices such as human-to-human knowledge transfer among the workers. It will increase firm-level knowledge base that will positively contribute to organizational competitiveness. In addition, such practices can evade the hostile effect of knowledge leakage.

Originality/value

The conceptual model is novel as this is the first study to establish (1) the empirical relationship of knowledge-oriented HR management practices and organizational competitiveness and (2) the moderating effect of knowledge-oriented HR management practices between knowledge leakage and organizational competitiveness.
Signaling sustainability: impact that learning how to report has on enrollment, endowment and emissions of North American higher education institutions
Authors: Minutolo Marcel C. , Ivanova Albena , Cong Michelle
Published: March 2021

Purpose

The purpose of this paper is to develop an integrated model assessing the frequency and timing between reports on the Association for the Advancement of Sustainability in Higher Education (AASHE) Sustainability Tracking, Assessment and Rating System (STARS) reporting the framework by higher education institutions (HEIs) and the relationship between the STARS score and reputation (enrollment), finances (endowment) and performance (emissions).

Design/methodology/approach

The development of the theoretical model is based on learning, signaling and legitimacy theories. This study collects data from the AASHE STARS to indicate the rating level of 202 HEIs, control variables, enrollment, endowments and emissions. The hypotheses were tested using generalized linear models.

Findings

Findings suggest that as HEIs report on their sustainability activity, they learn to report better but that there is also an “un-learning” aspect if the HEI skips reporting in a period. The results support the main hypothesis that there is a relationship between reporting and engagement with the HEIs in the form of enrollment and endowments. Finally, the findings provide evidence that the HEIs’ reporting is associated with a reduction in emissions.

Practical implications

The findings suggest that HEIs should develop a reporting strategy on a standardized framework such as AASHE STARs and they ought to codify the approach to learn from prior reporting. Students and alumni are increasingly seeking to engage the HEI in the sustainability process and the report is a mechanism for signaling activities.

Social implications

The findings suggest that AASHE STARS scores may be used by HEIs as a signaling mechanism to stakeholders of their commitment to sustainability. The signal is a mechanism to reduce information asymmetry between the HEI and stakeholders who may want more information on the institution’s attempts toward sustainability but lack access to information. Further, HEI partners have a mechanism to assess the overall level of commitment of the HEI toward sustainability and can, therefore, engage accordingly.

Originality/value

There has been significant work on signaling theory and sustainability. However, the relationship between STARs reporting as a signal that legitimates the HEI, learning how to report well and HEI performance has received less attention. The current study demonstrates that the STARS framework as a reporting mechanism signals the HEIs’ level of commitment to sustainability thereby legitimating it resulting in improved performance.
Developing network adequacy standards for VA Community Care
Authors: Mattocks Kristin M. , Elwy A. Rani , Yano Elizabeth M. , Giovannelli Justin , Adelberg Michael , Mengeling Michelle A. , Cunningham Kristin J. , Matthews Kameron L.
Published: March 2021

Objectives

To inform how the VA should develop and implement network adequacy standards, we convened an expert panel to discuss Community Care Network (CCN) adequacy and how VA might implement network adequacy standards for community care.

Data Sources/Study setting

Data were generated from expert panel ratings and from an audio‐recorded expert panel meeting conducted in Arlington, Virginia, in October 2017.

Study Design

We used a modified Delphi panel process involving one round of expert panel ratings provided by nine experts in network adequacy standards. Expert panel members received a list of network adequacy standard measures used in commercial and government market and were provided a rating form listing a total of 11 measures and characteristics to rate.

Data Collection Methods

Items on the rating form were individually discussed during an expert panel meeting between the nine expert panel members and VA Office of Community Care leaders. Attendees addressed discordant views and generated revised or new standards accordingly. Recorded audio data were transcribed to facilitate thematic analysis regarding opportunities and challenges with implementing network adequacy standards in VA Community Care.

Principal Findings

The five highest ranked standards were network directories for Veterans, regular reporting of network adequacy data to VA, maximum wait time/distance standards, minimum ratio of providers to enrolled population, and qualitative assessments of network adequacy. During the expert panel discussion with VA Community Care leaders, opportunities and challenges implementing network adequacy standards were highlighted.

Conclusions

Our expert panel shed light on priorities for network adequacy to be implemented under CCN contracts, such as developing comprehensive provider directories for Veterans to use when selecting community providers. Remaining questions focus on whether the VA could reasonably develop and implement network adequacy standards given current Congressional restraints on VA reimbursement to community providers.
A portable library of phosphate‐depletion based synthetic promoters for customable and automata control of gene expression in bacteria
Authors: Torres‐Bacete Jesús , Luís García José , Nogales Juan
Published: March 2021

Industrial biotechnology gene expression systems relay on constitutive promoters compromising cellular growth from the start of the bioprocess, or on inducible devices, which require manual addition of cognate inducers. To overcome this shortcoming, we engineered an automata regulatory system based on cell‐stress mechanisms. Specifically, we engineered a synthetic and highly portable phosphate‐depletion library of promoters inspired by bacterial PHO starvation system (Pliar promoters). Furthermore, we fully characterized 10 synthetic promoters within the background of two well‐known bacterial workhorses such as E. coli W and P. putida KT2440. The promoters displayed an interesting host‐dependent performance and a wide strength spectrum ranging from 0.4‐ to 1.3‐fold when compared to the wild‐type phosphatase alkaline promoter (PphoA). By comparing with available gene expression systems, we proved the suitability of this new library for the automata and effective decoupling of growth from production in P. putida. Growth phase‐dependent expression of these promoters could therefore be activated by fine tuning the initial concentration of phosphate in the medium. Finally, the Pliar library was implemented in the SEVA platform in a ready‐to‐use mode allowing its broad use by the scientific community.
Petrogenesis and Tectonic Implications of Jurassic Granites in the Xingcheng Area, Northeastern North China Craton
Authors: MU Maosong , YANG Debin , XU Wenliang , QUAN Yikang , HAO Leran , YANG Haotian , WANG Anqi
Published: March 2021

New integrated geochemical studies are reported for Jurassic granites of the Xingcheng area in the northeastern North China Craton. U–Pb zircon data indicate that the Huashan and Taili monzogranites were emplaced during the Early (189 ± 2 Ma) and Late (155 ± 1 Ma) Jurassic, respectively. They are typical of high‐K calc‐alkaline series rocks and I‐type granites, according to our whole‐rock geochemical researches. Both Early and Late Jurassic monzogranites show adakitic rock characteristics because of their high Sr contents (221–347 ppm) and Sr/Y ratios (28.7–37.5), and low Y contents (7.83 –14.7 ppm). The Early Jurassic monzogranite samples have an (87Sr/86Sr)i ratio of 0.7046, ∊Nd(t) values of –11.62 to –11.51, and ∊Hf(t) values of –13.6 to –6.4, whereas the Late Jurassic monzogranites have higher (87Sr/86Sr)i ratios of 0.7069–0.7071 and lower ∊Nd(t) (–20.65 to –20.46) and ∊Hf(t) (–27.6 to –20.0) values. We suggest that the Early Jurassic adakitic rocks were derived from partial melting of thickened lower crust contaminated with mantle‐derived materials, related to subduction of the Paleo‐Pacific Plate. The Late Jurassic adakitic rocks were derived from partial melting of thickened lower crust in an extensional tectonic setting associated with an active continental margin.
Muscle fibre distribution in forelimb, hindlimb and trunk muscles in three bat species: The little Japanese horseshoe, greater horseshoe and Egyptian fruit
Authors: Luziga Claudius , Miyata Hirofumi , Nagahisa Hiroshi , Oji Takashi , Wada Naomi
Published: March 2021

This study characterised muscle fibres in trunk, forelimb and hindlimb muscles of three bat species: little Japanese horseshoe (Rhinolophus cornutus), greater horseshoe (Rhinolophus ferrumequinum) and Egyptian fruit (Rousettus aegyptiacus). Twenty‐seven muscles from trunk, forelimb and hindlimb were dissected, weighed and analysed by immunohistochemistry and sodium didecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and determined their cross‐sectional areas (CSA). Results showed that Type IIa and Type IIa/x made the highest proportion of total muscle mass. Moderate proportion was formed by Type IIb. Type I and IIx appeared at very low levels in all bats. Type IIb was the only fibre type detected in patagial muscles in wing membrane of greater horseshoe while other fibre types were not observed. Type I muscle fibres were very few and appeared infrequently in fifteen muscles of Egyptian fruit and in only one muscle in each, greater horseshoe and little Japanese horseshoe. Type IIx was also detected in three muscles in greater horseshoe and only one muscle in Egyptian fruit but none in little Japanese horseshoe. The highest average CSA μm2 was detected in Type IIb and values were 734.2μm2 for LHB; 1537.9μm2 for GHB and 1,720.9μm2 for EFB. Lowest and undetermined values were observed for Type I and IIx. These data demonstrate that Type IIa, IIa/x and IIb form significant proportion of adult bat muscle mass and Type IIb is the largest fibre type. The distribution pattern is suggestive of specialised functions of the fibres in relation to orientation and speed of bats during flight.
Attitude toward personal genomics: A nation‐wide survey of public and professionals in Pakistan
Authors: Ilyas Muhammad , Malik Saima , Alam Mukhtar , Mahmood Aamir , Irfan Muhammad , Shah Muttahid , Rahman Atiqur , Ahmad Habib
Published: March 2021

With the emergence of modern genetic testing and profiling techniques, it has become imperative to assess the general public awareness and attitudes toward such developments. The public's perspective and possible responses are necessary for planning commercial, legal, medical, or healthcare initiatives. The purpose of this study was to assess the perception of the general public and professionals about the personal genome testing and genetic profiling. A questionnaire‐based survey was conducted to investigate the attitudes of 2954 adults (56.4% male and 43.6% female) from more than 120 different educational, research, and professional organizations of Pakistan. The aim of the study was to assess interest in genomic testing. The findings of this survey will feed into the larger Genome Projects in Pakistan and will be helpful for the national bioethical committee, healthcare agencies, diagnostic companies, and other institutions for making policy decisions.
Fields from Afar: Evidence of Heterogeneity in United States Corn Rotational Response from Remote Sensing Data
Authors: Pates Nicholas J. , Hendricks Nathan P.
Published: March 2021

We construct estimates of own‐ and cross‐price corn rotation elasticities using a field‐level dataset that accounts for over 83% of the US corn‐producing area. We allow rotational response to vary by estimating separate models across 115 subsamples that we delineate using Major Land Resource Areas (MLRAs) and soil characteristics. The results show a high degree of rotational response heterogeneity. Across the country, we find that rotational response is elastic in some areas and near zero in others. After aggregating the results to the national level, we find that modeling rotational response without allowing for heterogeneity produces a short‐run own‐price elasticity of corn planting of around 0.50, which conforms to the latest estimates in the literature. When allowing heterogeneous price sensitivity, our preferred estimate of the rotation elasticity is 0.69. This is evidence that imposing a uniform rotation response could seriously bias aggregate elasticity estimates.
Time interval from transurethral resection of bladder tumour to bacille Calmette–Guérin induction does not impact therapeutic response
Authors: Hensley Patrick J. , Bree Kelly K. , Brooks Nathan , Matulay Justin , Li Roger , Nogueras González Graciela M. , Navai Neema , Grossman Herbert B. , Dinney Colin P. , Kamat Ashish M.
Published: March 2021

Objectives

To investigate bacille Calmette–Guérin (BCG) tolerability and response with respect to the timing of BCG administration after transurethral resection of bladder tumour (TURBT) in patients with non‐muscle‐invasive bladder cancer (NMIBC).

Patients and Methods

A review of patients with NMIBC at our institution managed with at least ‘adequate BCG’ (defined by the United States Food and Drug Administration as at least five of six induction instillations, with two additional instillations comprising either maintenance or repeat induction) at our institution from 2000 to 2018 was performed. Time from TURBT to first instillation of induction BCG was stratified by quartile and analysed as a continuous variable. Kaplan–Meier and log‐rank tests analysed differences in recurrence‐free (RFS) and progression‐free survival (PFS). Cox proportional hazards regression models identified associations between risk factors and survival outcomes.

Results

A total of 518 patients received adequate BCG at a median (range) of 26 (6–188) days from TURBT. Overall, 45 patients (9%) developed BCG intolerance at a median (range) 12 (7‐33) instillations. When time from TURBT to BCG was stratified into quartiles, there was no difference with respect BCG intolerance (P = 0.966), RFS (P = 0.632) or PFS (P = 0.789). On both uni‐ and multivariate regression analysis for RFS and PFS, time from TURBT to BCG was not a significant predictor when analysed by quartile or as a continuous variable (the hazard ratio for RFS was 1.00, 95% confidence interval [CI] 0.99–1.00, P = 0.449; and for PFS was 0.99, 95% CI 0.98–1.00, P = 0.074).

Conclusion

The rates of tolerability and response to adequate BCG are not predicated by the timing of induction BCG instillation after TURBT. Early administration in properly selected patients is safe and delays do not affect therapeutic response.
Influence of carbon black with different polar groups on the solvent N‐methylmorpholine N‐oxide
Authors: Jin Hong , Kumi Alex Kwasi , Cui Shiqiang , Zhang Yumei
Published: March 2021

To confirm the effect of the surface property of carbon black (CB) on the lyocell process and the chemical stability of the solvent N‐methylmorpholine N‐oxide (NMMO), molecular dynamics simulation and ultraviolet tests were performed to investigate the interaction between aqueous NMMO solution and CB surfaces with different polar groups. The hydrophobic interaction between the O2 atom of NMMO and the unmodified CB surface increased with an increase in NMMO concentration. The interaction improved the dispersion of CB in aqueous NMMO solution, but this effect was not sufficient to prevent the aggregation between CB particles. Modifying the CB surface with a 1%‐3% carboxyl or amino group produced a stronger electrostatic interaction between the polar groups and the solvent molecules; however, the carboxyl group had a significant influence on the chemical stability of NMMO. The amino group can realise the stable dispersion of CB in aqueous NMMO solutions without affecting the chemical stability of NMMO, which would be the best choice for preparation of functional lyocell fibre.
6‐year results of BiOSS stents in coronary bifurcation treatment
Authors: Gil Robert J. , Kern Adam , Formuszewicz Radoslaw , Iñigo Garcia Luis A. , Dobrzycki Slawomir , Vassilev Dobrin , Bil Jacek
Published: March 2021

Background

The wide variation in bifurcation anatomy has generated an ongoing search for stents explicitly designed for coronary bifurcations, and to date, results have been underachieved.

Methods

The POLBOS I and POLBOS II were international, multicentre, randomized, open‐label, controlled trials. Patients were randomly assigned to BiOSS Expert (in POLBOS I, biodegradable polymer eluting paclitaxel)/BiOSS LIM (in POLBOS II, biodegradable polymer eluting sirolimus) stent implantation or regular drug‐eluting stent (rDES) deployment. A provisional T‐stenting strategy was the default treatment option. The primary endpoint of this pooled data study was the cumulative rate of major adverse cardiovascular events (MACE) consisting of cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR). Telephone follow‐up was performed annually up to 72 months. (ClinicalTrials.gov Identifier: POLBOS I—NCT02192840, POLBOS II—NCT02198300).

Results

The total study population consisted of 445 patients, 222 patients in the BiOSS group and 223 patients in the rDES group. The follow‐up rate was 93.7% in the BiOSS group and 91.9% in the rDES group. At 72 months, there was no significant difference between BiOSS and rDES groups regarding MACE (25.7% vs 25.1%, HR 1.06, 95% CI 0.73‐1.52), cardiac death (3.1% vs 4.0%, HR 0.94, 95% CI 0.43‐2.34), MI (3.6% vs 4.9%, HR 0.76, 95% CI 0.32‐2.89), TLR (18.9% vs 16.1%, HR 1.17, 95% CI 0.75‐1.83) and stent thrombosis rates (0.9% vs 0.5%, HR 1.21, 95CI 0.75‐2.09).

Conclusions

At the 6‐year follow‐up, clinically significant clinical events did not differ between BiOSS stents and rDES.
Entrepreneuring for deprived urban communities: Exploring the role of micro‐entrepreneurship
Authors: Colovic Ana , Schruoffeneger Marion
Published: March 2021

This paper studies how micro‐entrepreneurs engage in entrepreneuring to generate social value for their communities. We study three cases of micro‐entrepreneurs operating in deprived urban communities in Brazil. Our findings reveal that micro‐entrepreneurs create social value by engaging in transformative, emancipatory, and connective entrepreneuring. We identify a three‐stage model of social value creation through entrepreneuring. We contribute to the literature by providing evidence of the emancipatory and transformative dimensions of entrepreneuring and extend understanding of this phenomenon to include the dimension of connectivity.
Valproate usage in pregnancy: An audit from the Kerala Registry of Epilepsy and Pregnancy
Authors: Seshachala Balaji B. , Jose Manna , Lathikakumari Arya M. , Murali Sruthy , Kumar Arjun S. , Thomas Sanjeev V.
Published: March 2021

Objective

This is an audit of the use of valproate (VPA) during pregnancy in women with epilepsy (WWE).

Methods

We identified all pregnancies exposed to VPA in the Kerala Registry of Epilepsy and Pregnancy between January 2010 and December 2019. Subjects' past usage of antiepileptic drugs (AEDs), seizure count before and during pregnancy, fetal outcome, and major congenital malformations (MCMs) were abstracted from the registry records. The presumed reason for usage of VPA was deducted from the clinical records.

Results

There were 221 pregnancies (17.75%) exposed to VPA (monotherapy,n= 149) during the audit period. The MCM rate for the completed pregnancies exposed to VPA was higher (n = 20, 10.36%) than that of VPA‐unexposed pregnancies (n = 39, 4.96%). The relative risk for MCM with VPA exposure was 2.1 (95% confidence interval = 1.24–3.48, number needed to treat with VPA to result in MCM = 19). Reasons for using VPA during pregnancy (some women had more than one reason) were (1) VPA was the first AED prescribed and was effective (68, 29.06%), (2) other AEDs were ineffective (128, 54.70%), and (3) other AEDs were discontinued due to adverse effects (17, 7.28%). Other reasons (21, 8.97%) were (1) VPA was selected after the epilepsy classification was revised (3, 1.28%), (2) other AEDs were expensive (2, .85%), and (3) patient switched to VPA from other AEDs for unspecified reason (16, 6.83%). VPA was discontinued during pregnancy for 6 (2.71%) persons. Less than 10% of women were tried on lamotrigine or levetiracetam before switching to VPA.

Significance

Nine MCMs per thousand pregnancies can be avoided if VPA is not used in WWE. Safe and effective AEDs as alternatives to VPA are the need of the hour. Professional bodies and regulatory authorities need to implement updated guidelines on AED usage in girls and women.