bluuebunny/crossref_metadata_2025 huggingface dataset:
The crisprVerse: a comprehensive Bioconductor ecosystem for the design of CRISPR guide RNAs across nucleases and technologies
Authors: Hoberecht Luke , Perampalam Pirunthan , Lun Aaron , Fortin Jean-Philippe
Published: April 2022

The success of CRISPR-mediated gene perturbation studies is highly dependent on the quality of gRNAs, and several tools have been developed to enable optimal gRNA design. However, these tools are not all adaptable to the latest CRISPR modalities or nucleases, nor do they offer comprehensive annotation methods for advanced CRISPR applications. Here, we present a new ecosystem of R packages, called crispr-Verse, that enables efficient gRNA design and annotation for a multitude of CRISPR technologies. This includes CRISPR knockout (CRISPRko), CRISPR activation (CRISPRa), CRISPR interference (CRISPRi), CRISPR base editing (CRISPRbe) and CRISPR knockdown (CRISPRkd). The core package, crisprDesign, offers a comprehensive, user-friendly, and unified interface to add on- and off-target annotations via several alignment methods, rich gene and SNP annotations, and a dozen on- and off-target activity scores. These functionalities are enabled for any RNA- or DNA-targeting nucleases, including Cas9, Cas12, and Cas13. We illustrate the general applicability of our tools by designing optimal gRNAs for three case studies: tiling CRISPRbe library for BRCA1 using the base editor BE4max, tiling RNA-targeting libraries for CD46 and CD55 using CasRx, and activation of MMP7 using CRISPRa. The crisprVerse ecosystem is open-source and deployed through the Bioconductor project to facilitate its use by the CRISPR community (https://github.com/crisprVerse).
A Prospective Study to Improve Automated Blood Culture Diagnostics in Gram-Negative Sepsis by Implementing a “Diagnostic Stewardship Care-Bundle”
Authors: Gupta Ayush , Siddiqui Farha , Purwar Shashank , Saigal Saurabh , Sharma Jai Prakash , Kumar Sanjeev
Published: April 2022

Objectives

We implemented a diagnostic stewardship care-bundle (DSB): “Sepsis-48” with the aim of evaluating its impact on changes in duration of key steps in automated blood culture diagnostics (aBCD), compliance to care-bundle and turnaround time (TAT).

Methods

In this prospective study, a care-bundle checklist for automated blood culture bottles (BCBs) received from adult intensive care units (AICUs) was implemented between July 2020-June 2021 (intervention period, P2) and compared with a retrospective, pre-intervention period (P1) between March-June 2020. Microbial identification in positive BCBs with gram-negatives (+nBCBs) was enabled by inoculating conventional biochemical tests directly (dID) and direct antimicrobial susceptibility testing (dAST) was done as per EUCAST RAST standard. Clinical reports were issued only if a RAST reportable gram-negative was identified in dID.

Results

We observed significant reductions in the Loading time (LT) [63.5 (104.5-24.5) vs 32 (55-14) minutes, P<0.001] & time to dID+dAST performance (TTD) [186 (288.25-202.25) vs 115 (180-68) minutes, P=0.0018] in +nBCBs received from AICUs during P2. There was a significant increase in compliance to the bundle targets [LT≤45: 44% vs 66%, P=.006 and TTD≤120: 34% vs 51.7%, P=.03] during P2 (Table 2). Using dID+dAST method, provisional results could be read ∼13 hours earlier than those generated by VITEK®. Similar improvements were also noted for +nBCBs received from other locations.

Conclusions

The “diagnostic stewardship care-bundle” strategy to improve aBCD was successfully implemented leading to significant reductions in duration of targeted steps. Laboratories should implement “diagnostic stewardship care-bundles” as per their needs to improve microbiological diagnostics.
CaV3.1 T-type calcium channels regulate spatial memory processing in the dorsal subiculum
Authors: Joksimovic Srdjan M. , Ghodsi Seyed Mohammadreza , Heinsbroek Jasper A. , Orfila James E. , Busquet Nicolas , Tesic Vesna , Valdez Robert , Fine-Raquet Brier , Jevtovic-Todorovic Vesna , Raol Yogendra H. , Herson Paco S. , Todorovic Slobodan M.
Published: April 2022

The dorsal subiculum (dSub) is one of the key structures responsible for the formation of hippocampal memory traces but the contribution of individual ionic currents to its cognitive function is not well studied. Although we recently reported that low-voltage-activated T-type calcium channels (T-channels) are crucial for the burst firing pattern regulation in the dSub pyramidal neurons, their potential role in learning and memory remains unclear. Here we used in vivo local field potential recordings and miniscope calcium imaging in freely behaving mice coupled with pharmacological and genetic tools to address this gap in knowledge. We show that the CaV3.1 isoform of T-channels is critically involved in controlling neuronal activity in the dSub in vivo. Altering burst firing pattern by inhibiting T-channel activity markedly affects calcium dynamics, synaptic plasticity, neuronal oscillations and phase-amplitude coupling in the dSub, thereby disrupting spatial learning. These results provide a crucial causative link between the CaV3.1 channels, burst firing activity of dSub neurons and memory processing, thus further supporting the notion that changes in neuronal excitability regulate memory trace formation. We posit that subicular CaV3.1 T-channels could be a promising novel drug target for cognitive disorders.
Caveolae couple mechanical stress to integrin recycling and activation
Authors: Lolo Fidel-Nicolás , Pavón Dácil M. , Grande-García Araceli , Elósegui-Artola Alberto , Segatori Valeria Inés , Sánchez-Perales Sara , Trepat Xavier , Roca-Cusachs Pere , del Pozo Miguel A.
Published: April 2022

Cells are subjected to multiple mechanical inputs throughout their lives. Their ability to detect these environmental cues is called mechanosensing, a process in which integrins play an important role. During cellular mechanosensing, plasma membrane (PM) tension is adjusted to mechanical stress through the buffering action of caveolae; however, little is known about the role of caveolae in early integrin mechanosensing regulation. Here, we show that Cav1KO fibroblasts increase adhesion to FN-coated beads when pulled with magnetic tweezers, as compared to wild type fibroblasts. This phenotype is Rho-independent and mainly derived from increased active β1-integrin content on the surface of Cav1KO fibroblasts. FRAP analysis and endocytosis/recycling assays revealed that active β1-integrin is mostly endocytosed through the CLIC/GEEC pathway and is more rapidly recycled to the PM in Cav1KO fibroblasts, in a Rab4-dependent manner. Moreover, the threshold for PM tension-driven β1-integrin activation is lower in Cav1KO MEFs than in wild type MEFs, through a mechanism dependent on talin activity. Our findings suggest that caveolae couple mechanical stress to integrin cycling and activation, thereby regulating the early steps of the cellular mechanosensing response.
Understanding the determinants of consumers' reverse exchange intention as an approach to e-waste recycling: a developing country perspective
Authors: Sabbir Md. Mahiuddin , Khan Tahsin Tabish , Das Amit , Akter Sharmin , Hossain Md. Alamgir
Published: April 2022

Purpose

End-of-life electronic products exchange (EEPE) program could be an effective approach to e-waste recycling that requires consumers' participation. Thus, it is highly recommended to study factors stirring consumer behavior with regard to EEPE programs, which is largely under-explored in the existing literature. Hence, grounding on the Theory of Planned Behavior (TPB) and Attitude-Behavior-Context (A-B-C) model, this study attempts to understand the determinants of consumers' EEPE intention by adding contextual and non-cognitive factors to the proposed research model.

Design/methodology/approach

Employing a purposive sampling technique, respondents were drawn from university students and general consumers of electronic products in a developing country. Factor analysis, structural equation modeling (SEM) and SPSS PROCESS were used to analyze the collected data.

Findings

Empirical results confirm that subjective norm has the strongest positive impact on EEPE intention. Following this, attitude toward EEPE and perceived behavioral control play positive mediating roles in determining EEPE intention. Moreover, government initiatives moderate the unsolicited “attitude–intention gap”.

Practical implications

Drawing on this study's outcomes, the study urges to form comprehensive awareness-building campaigns, rules and regulations regarding proper e-waste management, promote “exchange offer” programs and educational programs to encourage EEPE.

Originality/value

This study makes two fresh contributions to the extant literature. First, by coupling the TPB and A-B-C theory, this study showed that both attitude (i.e. attitude toward EEPE) and context (i.e. government initiatives) are essential in eliciting individual-level post-consumption pro-environmental behavior (PEB) (i.e. EEPE). Second, government initiatives elucidate the attitude–intention gap in the reverse logistics context, especially in developing countries.
The impact of optimal parcel locker locations on costs and the environment
Authors: Peppel Marcel , Spinler Stefan
Published: April 2022

Purpose

Last-mile delivery is associated with a negative environmental impact and high costs. The purpose of this paper is to develop an approach to designing stationary parcel locker (SPL) networks while minimizing both CO2 equivalent (CO2e) emissions and costs during delivery and pick-up.

Design/methodology/approach

This study uses a multinomial logit model to evaluate recipients' willingness to use SPLs based on their availability at home and travel distance. To determine optimal SPL locations, this study formulates a mixed-integer linear programming model.

Findings

The empirical study of different regional clusters reveals that optimal SPL locations can generate cost savings of up to 11.0%. SPLs have a positive impact on total CO2e emission savings in urban areas (i.e. up to 2.5%), but give rise to additional emissions (i.e. 4.6%) in less populated areas due to longer travel distances during the pick-up process.

Originality/value

This paper optimizes SPL locations and the ecological effect of SPLs by minimizing emissions and costs simultaneously. Furthermore, it extends existing discrete choice models by also including recipients' availability at home, increasing the accuracy of recipients' preferences. So far, the effect of SPLs has been studied for metropolitan areas only. A global logistics service provider shared a real dataset which allows us to study seven different regional clusters ranging from rural areas to large cities. Thus, this study contributes to the field of sustainable urban logistics.
What brings the state back in? An examination of contracting reversal
Authors: Hung Wan-Ju , Lu Jiahuan
Published: April 2022

Purpose

In recent years, there is a steady increase of studies documenting the emergence of “contracting back-in” in many countries around the world, that is, governments bringing previously contracted services back in-house and once again relying on public employees to deliver these services. Through a survey of the academic discourse on contracting back-in, this manuscript describes the phenomenon of contracting back-in and discusses its implications for “bringing the state back in”.

Design/methodology/approach

The manuscript conducts a systematic review of existing literature on contracting back-in with a focus on the scope and rationale of contracting back-in.

Findings

The existing literature demonstrates that contracting back-in is often as common as contracting out and can be found in a variety of countries and across different service areas. Existing studies also suggest that contracting back-in is driven by a mix of managerial, political, and environmental factors. The rise of contracting back-in could imply a revival of the administrative state in public governance and a more dynamic, potentially more complicated, system of public service delivery.

Originality/value

The manuscript contributes to the special issue on “bringing the state back in” through the lens of government contracting. It adds a number of implications to the discussion on the emergence of the “new” administrative state and strategies to reinvent it.
An ensemble design of a cash crops-warehouse receipt system (WRS) based on blockchain smart contracts
Authors: Shao Deo , Kombe Cleverence , Saxena Stuti
Published: April 2022

Purpose

Warehouse receipt system (WRS) schemes aim to revitalize the market of cash crops, particularly those of the smallholder farmers. However, the existing government schemes for the smallholder farmers have not been much successful on account of issues related with transparency and trust deficit, thereby limiting farmers' access to credit for their farming activities as channeled via the formal financial institutions. Conceding that blockchain is an emerging technology, this study aims to theoretically posit the potential to optimize WRS in real time to bolster farmers' trust and privacy.

Design/methodology/approach

The research bases itself on the design science research (DSR) approach. Using the DSR approach backed by the literature review and evolutionary prototyping, a blockchain-based WRS has been advanced in the study.

Findings

This study provides a design of a digital WRS, which serves as a proof of concept of blockchain technology (BCT) applications in improving transparency in the WRS in the agricultural sector. The findings from this study present the possibility of leveraging blockchain smart contracts to improve the linkages between the WRS stakeholders to promote trust and transparency that would eventually unlock the potentials of WRS schemes. Furthermore, the findings inform decision-makers and practitioners to prioritize the emerging technologies in revamping the classical WRS.

Research limitations/implications

The study leaves research pointers for implementing BCT in agricultural supply chain and furthering the findings from the present study with an empirical agenda.

Originality/value

Whilst research on the BCT applications across myriad sectors abounds, research on the BCT applications to address societal needs is conspicuously limited. Furthermore, research on the practical implementation of the BCT in real-world scenarios is few and far between. The present study seeks to plug these gaps by underlining the application and utility of blockchain in WRS. The study makes a significant contribution to the theory and practice of the agrarian supply chain management, specifically the WRS, by invoking design knowledge obtained through an iterative design process besides serving as an edifice for the integration of emerging technologies, notably BCT in the agricultural sector.
Intention of postgraduate students towards the online education system: application of extended technology acceptance model
Authors: Sinha Abhijit , Bag Sudin
Published: April 2022

Purpose

The study is done to investigate the factors that affect the intention of higher education students towards online education. The research also focuses on the importance of students' stability and students' resilience on perceived usefulness and perceived easiness of use that frame the attitude towards the intention to use online education.

Design/methodology/approach

Online survey method is employed using Google form link with a sample of 686 students of higher education. Excluding the outliers (univariate and multivariate), the final sample size (N = 679) considers the empirical results of the study. Partial least square structural equation modelling (PLS-SEM) is applied to unearth the relationship in the proposed research model of the study.

Findings

The empirical results indicate that perceived usefulness and perceived easiness of use have a direct impact on students' intention to use online education platform. Moreover, perceived usefulness and perceived easiness of use also have a positive influence on the students' attitude, which has a strong influence on students' intention to use online mode of education system. Also, students' stability and students' resilience have mixed impact on the level of perceived usefulness and perceived easiness of use that are the most useful determinants of attitude towards the intention to use online education.

Research limitations/implications

The study counts on the technology acceptance model (TAM) where constructs like behavioural controllability, past exposure and perceived accordance are not considered for measuring the intention of students in adapting to online education.

Originality/value

This paper employs the extended model of technology acceptance with additional determinants, namely, students' stability and students' resilience, to investigate the intention to use the online form of education as an alternative to the offline mode.
Gamifying piracy: functions and users of the Z-library
Authors: Kjellström Zakayo
Published: April 2022

Purpose

This paper aims to show how an illegal repository of literature, the Z-library, relates to and influences its users and how this relation is unique due to the illegal nature of the platform. The paper utilizes the idea of gamification to exemplify how to motivate users to contribute to a large shadow library in order to create the “world's largest e-book library,” sans “librarians.”

Design/methodology/approach

The study makes use of an ethnographic approach. It interrogates the functions of the website through intensive use—a close reading of sorts. The data provide a foundation for illustrating how illegal text repositories function at a surface level and how their design appeals to their user-base.

Findings

The paper provides a thorough and non-biased overview of how a “black open access” or “shadow library” site provides its users with pirated literature. It suggests that the lynchpin sustaining their functionality is a gamification of piracy designed to motivate a fragmented collective of individuals who work primarily for personal reward, rather than altruistic goals.

Research limitations/implications

Due to the design of the study, the findings are not universal or applicable to all illegal repositories of text. Readers and researchers are encouraged to apply the concept introduced here to other cases.

Social implications

This paper includes implication on the perception of literature piracy, how pirated literature is distributed and who performs the labor required to sustain illicit text repositories.

Originality/value

This paper provides a novel conceptual basis to study literature piracy.
High school change: a reflective essay on three decades of frustration, struggle and progress
Authors: Hargreaves Andy
Published: April 2022

Purpose

The purpose of this essay is to honor, position and reflect on key themes related to high school reform within the careerlong scholarship of Karen Seashore Louis. It is presented in relation to my own and others' key studies and book-length arguments regarding educational change, knowledge utilization, professional communities and innovation, over the past 30 years and up to the present time.

Design/methodology/approach

The article examines and interprets major works by Karen Seashore Louis and other educational change theorists that address repeated systemic failures, and episodic outlier efforts, at transformational change in high schools.

Findings

High school change has only failed if it is judged by the overarching criterion of system-wide transformation. Fair assessments of high school change must also examine accumulated incremental innovations. In light of the need for transformational aspirations in schools to mesh with transformational directions in society, the global pandemic and its aftermath may provide five key opportunities for long-awaited transformation.

Originality/value

There are different levels and degrees of innovation. Incremental innovation is as important as wholesale transformation. The growing number of networked outliers of innovation raises questions about the false equation of whole system change with bureaucratic state reform. Although the influential literature on whole system change is rooted in a small number of English-speaking countries, transformational change on a system-wide basis already exists in Northern Europe and parts of the Global South. Last, the pandemic and other major disruptions to the global social order have produced conditions that are highly favorable to transformational change in the future.
CEO overconfidence and forecast accuracy moderated by CEOs' accounting-based attributes
Authors: Ben Ahmed Faten , Jarboui Anis
Published: April 2022

Purpose

The purpose of this paper is to focus on the moderating effect of CEO's accounting-based attributes on the relationship between chief executive officer (CEO) overconfidence and forecast accuracy in European companies.

Design/methodology/approach

Data from a sample of 347 European firms listed on Stoxx Europe 600 index from 2005 to 2018 are used to test the moderation model using moderation regression analysis.

Findings

Evidence reveals that CEO overconfidence is negatively associated with forecast accuracy. Further, CEO's accounting-based attributes significantly moderates the impact of CEO overconfidence on forecast quality.

Originality/value

This study is unique in providing European evidence for the moderating effect of CEO's accounting-based attributes on the relationship between CEO overconfidence and forecast quality. This paper is also relevant as it addresses the interaction between two sciences (psychology) to explain the forecast accuracy (accounting).
The impact of entrepreneurial firm social purpose on bank loan officer decisions: a study of loan covenant violations
Authors: Austin Rebekah , Weinberger Andrew Scott , Mohundro Jon
Published: April 2022

Purpose

Loan officer decisions are of particular importance to entrepreneurial firms which rely heavily on debt financing as a primary source of capital. The authors investigate whether social purpose in these firms impact loan officer response to the violation of a debt covenant and whether there is a differential response in decision making between loan officers that work at local banks and those that work at national banks.

Design/methodology/approach

In total 332 loan officers from cities in the South and Midwest United States participated in a quasi-experiment comparing entrepreneurial firms that violated their debt covenants. The loan officers were asked to evaluate loan materials and decide whether they would enforce loan covenant provisions of renegotiated interest rate and by what magnitude. In the treatment group, the loan officer evaluated loan materials of an entrepreneurial firm that included information related to the firms social purpose within their community. In the control group, the evaluation materials did not include this information.

Findings

Consistent with social capital theory, the results suggest that loan officers view community involvement as beneficial to entrepreneurial firm value. Loan officers were less likely to increase interest rates among firms that demonstrated social purpose. Loan officers that decided to increase interest rates punished socially purposeful firms less severely than non-socially purposeful firms. Additionally, loan officers at community banks were less likely to increase interest rates than those at national banks.

Originality/value

While the prior literature examines loan covenant violations, the authors focus on the impact of loan officer decision making in entrepreneurial firms specifically around covenant enforcement. Loan officer decisions have important implications for debt financing but are typically not observable to researchers. Prior work examining the relationship between social purpose and debt financing focuses on large public firms. This study recognizes that social purpose in entrepreneurial firms is less formalized and explicit and thus should be studied separately from large firms.
Dung beetles maintain phylogenetic divergence but functional convergence across a highly fragmented tropical landscape
Authors: Rivera Jose D. , Espinosa de los Monteros Alejandro , da Silva Pedro Giovâni , Favila Mario E.
Published: April 2022

Understanding how human‐modified landscapes affect the phylogenetic composition and assembly mechanisms of biological communities is critical for effectively managing and restoring tropical ecosystems. We evaluated how forest coverage loss, fragmentation and landscape heterogeneity affect the phylogenetic diversity of dung beetles and their assembly mechanisms in Los Tuxtlas Biosphere Reserve, a protected but highly fragmented tropical landscape.

We calculated Faith's phylogenetic diversity, mean pairwise phylogenetic distance and mean nearest taxon distance for 5,388 individuals in 36 species. The standardised effect sizes of these metrics were estimated to control their correlation with species richness. Phylogenetic diversity was also assessed separately for each dung beetle functional group. Finally, we compared the mean functional and phylogenetic pairwise distance and mean nearest taxon distance and measured the phylogenetic signal among dung beetle functional traits to determine the influence of niche conservatism on the phylogenetic structure of species assemblages.

Faith's phylogenetic diversity of dung beetles was positively correlated with forest coverage, while their mean phylogenetic and nearest taxon distance values decreased with increasing landscape fragmentation. Necrophagous beetles and forest specialists responded most negatively to forest coverage loss and fragmentation.

Alpha and beta diversity values showed phylogenetic overdispersion but functional convergence and weak phylogenetic signals in their functional traits, suggesting low niche conservatism. Landscapes with moderate forest coverage (≥40%) favoured higher phylogenetic beta diversity, whereas phylogenetic and functional beta diversity decreased significantly in landscapes with low forest coverage (<30%).

Synthesis and applications. Forest habitats in fragmented landscapes are essential for safeguarding the evolutionary history of dung beetles, reducing biotic homogenisation processes by favouring phylogenetic overdispersion and complementarity between sites. Therefore, to secure the phylogenetic diversity of dung beetles within fragmented tropical reserves, we recommend protecting the existing forests, preventing further fragmentation of continuous forest areas and increasing matrix quality by implementing biodiversity‐friendly production systems. Finally, managers should consider assessing different functional groups in other species, as their response to landscape disturbance may not be phylogenetically similar. The above will allow more effective management practices to protect the species most susceptible to disturbances.
Inhibition of mTOR by temsirolimus overcomes radio‐resistance in nasopharyngeal carcinoma
Authors: Huang Shiyong , Du Ke , Liu Zeng , Li Jiangping
Published: April 2022

Radio‐resistance is a leading cause of nasopharyngeal carcinoma (NPC) treatment failure and identification of sensitising therapeutic targets is an unmet need to enhance clinical management. Given that the mammalian target of rapamycin (mTOR) signalling confers resistance to cancer therapy, we investigated whether mTOR contributes to radio‐resistance in NPC and pharmacological inhibition of mTOR can overcome radio‐resistance. We found that mTOR mRNA and protein levels, and phosphorylation of its downstream effector were increased in radio‐resistant NPC compared with parental cells. mTOR inhibitor temsirolimus inhibits proliferation and induces apoptosis in a panel of NPC cell lines. Importantly, temsirolimus acts synergistically with radiation and is effective against radio‐resistant cells. Using radio‐resistant xenograft mouse model, we validated the efficacy of temsirolimus in preventing tumour formation and inhibiting tumour growth. Temsirolimus overcome radio‐resistance in NPC via inhibiting mTOR signalling. Our work provides the pre‐clinical evidence that the combination of radiation and mTOR inhibitor may be a therapeutic strategy in NPC. Our findings might accelerate the initiation of clinical trials on radio‐resistant NPC patients using temsirolimus.
Biographical accounts of the impact of fatigue in young people with sickle cell disease
Authors: Poku Brenda Agyeiwaa , Pilnick Alison
Published: April 2022

Children and young people (CYP) with sickle cell disease (SCD) are a 'missing voice' in the debate on biography and sociology of chronic illness, meaning we know little about the social consequences of the illness for CYP. This paper examines the meaning of fatigue (a common symptom) for adolescents with SCD. Analysing 24 in‐depth interviews with adolescents aged 12–17 years in Ghana, we draw on the distinction proposed by Bury (1988) between 'meanings as significance' and 'meanings as consequence' to examine biographical aspects of fatigue. We argue that concepts of 'biographical disruption' and 'normal illness' do not easily accommodate the experience of CYP with congenital chronic illnesses like SCD, as their sense of (un)disruption and normality/continuity is contextualised relative to normative expectations about what it is to be a young person. At biographical transition points, illness/symptoms present from birth may evolve, shift and become experienced as 'new', 'different', or 'non‐normal'. They may become restrictive rather than continuous or disruptive. These experiences are influenced primarily by normative biographical expectations and the pursuit of identity affirmations. We propose that biographical restriction, biographical enactment, biographical abandonment and biographical reframing are more relevant concepts for understanding the experiences of CYP living with SCD.
Cervical intraepithelial neoplasia in women with transformation zone type 3: cervical biopsy versus large loop excision
Authors: Gustafson Line Winther , Hammer Anne , Bennetsen Mary Holten , Kristensen Christina Blach , Majeed Huda , Petersen Lone Kjeld , Andersen Berit , Bor Pinar
Published: April 2022

Objective

To compare the proportion of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in cervical biopsies with that in large loop excision of the transformation zone (LLETZ) specimens in women aged ≥45 years with transformation zone type 3 (TZ3).

Design

Multicentre cross‐sectional study.

Setting

Three colposcopy clinics in the Central Denmark Region.

Population

Women aged ≥45 years referred to colposcopy as a result of a positive human papillomavirus (HPV) test and/or abnormal cytology and with TZ3 at colposcopy.

Methods

Women had multiple biopsies taken and an LLETZ was performed.

Main outcome measures

Histologically confirmed CIN2+ in biopsies compared with that in LLETZ specimens.

Results

Of 166 eligible women at colposcopy, 102 women with paired data from biopsies and LLETZ specimens were included for final analysis. The median age was 67.7 years (IQR 62.6–70.4 years), and most were postmenopausal (94.1%) and had undergone HPV‐based screening (81.3%). The CIN2+ detection rate was significantly higher in LLETZ specimens than in biopsies (32.4% vs 14.7%, difference 17.7%, 95% CI 6.3–29.0%), resulting in more than half of CIN2+ cases being missed in biopsies (54.5%, 95% CI 36.4–71.9%). The overall agreement between biopsies and LLETZ was 82.4% (95% CI 73.6–89.2%).

Conclusions

CIN2+ detection is underestimated in women aged ≥45 years with TZ3 if detection relies on the results of biopsies alone. To reduce the risk of underdiagnosis and overtreatment, future studies should explore the use of new biomarkers for risk stratification to improve discrimination between women at increased risk of CIN2+ who need to undergo LLETZ and women who may undergo follow‐up.
Phase 2 study of first‐line pembrolizumab monotherapy in elderly patients with non‐small‐cell lung cancer expressing high PD‐L1
Authors: Masuda Takeshi , Fujitaka Kazunori , Suzuki Tomoko , Hamai Kosuke , Matsumoto Naoko , Matsumura Mirai , Isoyama Shoko , Ueno Sayaka , Mito Mineyo , Yamaguchi Kakuhiro , Sakamoto Shinjiro , Kawano Reo , Masuda Ken , Nishino Ryohei , Ishikawa Nobuhisa , Yamasaki Masahiro , Hattori Noboru
Published: April 2022

Background

Pembrolizumab is the recommended first‐line therapy for patients with advanced non‐small‐cell lung cancer (NSCLC) and a programmed death ligand‐1 (PD‐L1) tumor proportion score (TPS) of ≥50% without driver mutations. However, its efficacy and safety for patients ≥75 years have not been prospectively investigated; this was the aim of this study.

Methods

This multicenter and open‐label single‐arm phase II study was conducted at 12 institutions. Chemotherapy‐naïve patients with advanced NSCLC and a PD‐L1 TPS of ≥50% without EGFR mutations or translocation of the ALK received pembrolizumab every 3 weeks. The primary endpoint was progression‐free survival (PFS) with a threshold of 4.3 months. The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life.

Results

Twenty‐six patients were enrolled between October 2017 and March 2020. The median PFS was 9.6 (95% confidence interval [CI] 2.1–20.6) months. The lower limit of the 95% CI did not exceed the target. The median OS was 21.6 months. The ORR and DCR were 41.7% and 70.8%, respectively. The proportion of patients with grade ≥3 treatment‐related adverse events was 15.4%. The quality of life score did not change significantly during treatment.

Conclusion

While this study showed that pembrolizumab was a tolerable treatment for elderly patients, the safety requires further confirmation in a larger study. Although the primary endpoint, the median PFS (9.6 months), was slightly shorter than that (10.3 months) of the previous phase III study (KEYNOTE‐024 study), the median PFS did not achieve the expected value.
Characteristics of dried fish stores: Evidence based on an intact pit from Late Islamic Qatar
Authors: Yeomans Lisa
Published: April 2022

Archaeological evidence for the preparation of preserved fish is common. Preserving fish allowed stockpiling of temporary abundance of food created by good catches and seasonal plenty. In traditional societies, the majority of fish caught are preserved for later use rather than consumed fresh. Ethnographic information from southeast Arabia, and the wider region, for the storage of fish provides interesting details of the process. Archaeological evidence for fish storage is not usually the stored product itself, but distinctive species and element composition of preparation waste or post‐consumption refuse. Archaeologists rarely excavate a complete cache of preserved fish. This study presents data from a fish storage pit, capped with a mud seal, excavated at the Late Islamic site of Freiha (al‐Furayḥa) in Qatar. The contents of the pit were intact providing an opportunity to examine the practice of storing dried fish from the product itself and compare this evidence to ethnographic accounts.
Acetate‐ versus lactate‐buffered crystalloid solutions: A systematic review with meta‐analysis and trial sequential analysis
Authors: Ellekjaer Karen Louise , Perner Anders , Sivapalan Praleene , Møller Morten Hylander
Published: April 2022

Objective

There is a widespread use of buffered crystalloid solutions in clinical practice. However, guidelines do not distinguish between specific types of buffered solutions and clinical equipoise exists. We aimed to assess the desirable and undesirable effects of acetate‐ versus lactate‐buffered solutions in hospitalised patients.

Methods

We conducted a systematic review with meta‐analysis and trial sequential analysis of randomised clinical trials assessing the use of acetate‐ versus lactate‐buffered solutions for intravenous administration in hospitalised adults and children. The primary outcome was all‐cause short‐term mortality. We adhered to our published protocol, the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) statement, the Cochrane Handbook and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology.

Results

We included five RCTs enrolling 390 patients. We found no statistically significant difference in short‐term mortality (random effects, risk ratio [RR] 0.29; 95% confidence interval [CI] 0.06–1.51, p = .14, I2 = 0%) or hospital length of stay (LOS) (random effects, mean difference [MD]—1.31, 95% CI −3.66 to 1.05, p = .28, I2 = 0%) between acetate‐ versus lactate‐buffered solutions. The quality of evidence was very low. Data regarding intensive care unit LOS were reported by three trials and duration of vasopressor treatment by one trial; none of these data allowed for pooling in meta‐analyses. No trials reported data on long‐term mortality, health‐related quality of life, adverse events, duration of mechanical ventilation or renal replacement therapy.

Conclusion

In this systematic review, we found very low quantity and quality of evidence on the use of acetate‐ versus lactate‐buffered solutions in hospitalised patients.
Serum concentration of oral midazolam as pediatric preanesthetic medication and factors related to the sedation level
Authors: Matsuda Hiromi , Takenaka Jungo , Kawabata Mariko , Komatsu Toshiaki , Sakanoue Kazumi , Atsuda Koichiro , Okamoto Hirotsugu
Published: April 2022

Background

Preanesthetic medication is important to eliminate surgical anxiety in pediatric patients and facilitate their smooth transfer to the operating room. Midazolam is the most commonly used preanesthetic medication. However, it has been reported that the sedative effect varies from patient to patient. In this study, the pharmacokinetics of midazolam were examined, and the aim was to assess the factors affecting the quality of sedation.

Methods

The participants were children ranging in age from 6 months to 8 years scheduled for surgery. Midazolam 0.5 mg/kg was administered orally 30 min before entering the operating room, and the sedation level was evaluated at the time of mask application. Blood was collected after slow induction, and the serum concentration of midazolam was measured using high‐performance liquid chromatography.

Results

A total of 98 patients were registered. There was no difference in serum concentrations between the effective sedation group and the ineffective sedation group (48.0 vs. 49.1 ng/mL), regardless of the effect of midazolam. Percentages of ineffective sedation by age (0 to 7 years) were 66.6%, 60%, 33.3%, 11.1%, 0%, 0%, 12.5%, and 0%, respectively. On multivariate logistic regression analysis, siblings (OR = 3.9, CI: 1.1–14.0, p = .03) and age (OR = 3.2, CI:1.2–8.5, p = .02) were related to an insufficient sedative effect.

Conclusion

The serum concentration of oral midazolam reached effective levels even in patients in whom the sedative effect was inadequate. It is important to manage the perioperative period with appropriate concurrent premedication taking into account patient age and social background characteristics.

Clinical trial registration

Clinical trial registry: UMIN R000052504.
Predictive factors of posterior corneal shift after small incision lenticule extraction: a 5‐year follow‐up study
Authors: Cao Huazheng , Zhang Lin , Liang Shuang , Chen Xuan , Jhanji Vishal , Wang Yan
Published: April 2022

Purpose

The aim of this study was to determine risk factors affecting changes in posterior corneal elevation (PCE) and predict the 5‐year stability after small incision lenticule extraction (SMILE).

Methods

This retrospective, longitudinal study enrolled 161 patients post‐SMILE. The PCE values were measured at the apex, thinnest, maximal and 24 other prespecified preoperative points and at 6 months, 1 year and 5 years postoperatively.

Results

Posterior corneas exhibited time‐dependent, region‐dependent and angle‐dependent changes. For every dioptre increase in the absolute preoperative spherical equivalent (SE), 10‐μm decrease in the central corneal thickness (CCT), 10‐μm increase in the maximum lenticule thickness (MLT), 10‐μm decrease in the residual bed thickness (RBT), 10% increase in the percentage ablation depth (PAD, MLT divided by CCT) and 10% decrease in the percentage stromal bed thickness (PSBT, RBT divided by CCT), PCE exhibited average forward displacements of 0.2–0.4, 0.2–0.7, 0.1–0.2, 0.1–0.3, 0.6–1.0 and 0.5–1.1 μm, respectively (p < 0.05). PSBT was the variable with the highest accuracy in predicting 5‐year stability of posterior corneas (area under curve = 0.75). The cut‐off values of SE, CCT, MLT, RBT, PAD and PSBT for increased PCE were −8.00 to −8.31 D, 481.0–498.5 μm, 139.5–144.5 μm, 255.5–263.5 μm, 26.9–28.3% and 48.9–52.6%, respectively.

Conclusion

Eyes with thinner corneas, higher myopia requiring greater MLT and lower RBT exhibited greater predispositions towards posterior protrusion. The thresholds for preventing forward posterior corneal displacement were 26.9–28.3% for PAD and 48.9–52.6% for PSBT. Prediction of posterior corneal stability is useful for assessing surgical risks post‐SMILE.
Preterm birth, poor foetal growth and anxiety disorders in a Finnish nationwide register sample
Authors: Ståhlberg Tiia , Upadhyaya Subina , Khanal Prakash , Sucksdorff Minna , Luntamo Terhi , Suominen Auli , Sourander Andre
Published: April 2022

Aim

We examined the associations between preterm birth, poor foetal growth and anxiety disorders among children and adolescents. Additionally, we examined the impact of common comorbidities and specific anxiety disorders separately.

Methods

Three Finnish registers provided data on a nationwide birth cohort of 22,181 cases with anxiety disorders and 74,726 controls. Conditional logistic regression was used to examine the associations.

Results

Extremely very preterm birth and moderate‐late preterm birth were associated with increased adjusted odds ratios (aOR) for anxiety disorders (aOR 1.39, 95% CI 1.11–1.75 and aOR 1.13, 95% CI 1.03–1.23, respectively). Weight for gestational age of less than −2SD (aOR 1.29, 95% CI 1.17–1.42) and −2SD to −1SD (aOR 1.08, 95% CI 1.03–1.14) were associated with increased odds ratios for anxiety disorders. When comorbidities were considered, the associations became statistically insignificant for pure anxiety disorders, but remained significant in the groups with comorbid depressive or neurodevelopmental disorders.

Conclusion

Preterm birth and poor foetal growth increased the odds for anxiety disorders. However, the associations seem to be explained by the conditions of comorbid depressive and neurodevelopmental disorders. Comorbidities should be considered when examining and treating child and adolescent anxiety disorders.
Governing a union's external stakeholders: A prioritization method based on relationship quality and perceived impact
Authors: Plaisance Guillaume
Published: April 2022

Stakeholder governance is a growing issue in the literature and for organizations. The complex and uncertain environment of nonprofit organizations forces them to prioritize stakeholder requirements. The traditional criterion of influence and power is nevertheless proving insufficient for these organizations, especially those in political or interest representation sectors. This article proposes to use the relationship quality with stakeholders and its components (trust, satisfaction, influence, engagement) as criteria for prioritization. The study is carried out within the “Young Farmers” union, a French 50,000‐member union defending the interests of agriculture and of farmers under 35 years of age. It questions external stakeholders on the relationship with the organization and its impact and it enables to verify the relevance of these criteria. The results suggest integrating stakeholder emotions into the same‐named theory and studying relationship quality as a process in which satisfaction builds trust that enables engagement, which itself has a positive role on influence. The findings also revisit strategic models of stakeholder prioritization by proposing the four components of relationship quality mentioned above as prioritization attributes. Finally, NPOs’ partners are invited to take into account the subjectivity of the evaluation process and thus to favor reasonable methods to avoid handicapping NPOs.
Robotic mitral valve plasty for isolated clefts of mitral valve leaflets
Authors: Ishikawa Norihiko , Watanabe Go , Miyata Kazuto , Shigematsu Sayaka , Horikawa Takafumi , Seguchi Ryuta , Kiuchi Ryuta , Tomita Shigeyuki , Ohtsuka Toshiya
Published: April 2022

A 21‐year‐old female patient referred to our institute had been suffering from severe mitral valve regurgitation due to a rare anomaly: a typical cleft at the posterior mitral leaflet and the other partial one at the anterior leaflet. We successfully fixed the mitral valve using the robot‐assisted totally endoscopic technique which could perform suture closure of both leaflets and annuloplasty. This communication is the first report of the robotic and totally endoscopic procedure which could treat this rare mitral anomaly.
The economic and trade effects of the UK–Korea free trade agreement on the United Kingdom, Korea, Japan, China, and the European Union
Authors: Yi Chae‐Deug
Published: April 2022

We explored a comparative static computable general equilibrium model with six regions and 12 sectors to estimate the impacts of the recent UK–Korea free trade agreement (FTA) along with the European Union (EU)–Korea FTA. The empirical results provide quantitative evidence of the impact on national GDP, national exports and imports by sector, and the changes in exports or imports among the United Kingdom, Korea, Japan, China, and the EU. The UK–Korea FTA, along with the EU–Korea FTA, increases GDP and welfare for the United Kingdom and Korea; moreover, there is a large increase in automobiles, transport equipment, and machinery exports between Korea and the United Kingdom. The GDP and welfare level of non‐member countries such as Japan and China will slightly decline. Exports from the United Kingdom and Korea to non‐member countries are also expected to decrease in most manufacturing sectors. The UK–Korea FTA will lead to increases in imports between the United Kingdom and Korea due to mutual trade creation effects and trade diversion effects. However, non‐member countries such as Japan's exports are expected to experience a large decline in automobiles to the United Kingdom and in most manufacturing products to Korea due to the negative impact of the UK–Korea FTA.