bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning to automate cryo-electron microscopy data collection with Ptolemy
Authors: Kim Paul T. , Noble Alex J. , Cheng Anchi , Bepler Tristan
Published: November 2022

Over the past decade, cryo-electron microscopy (cryoEM) has emerged as an important method for determining near-native, near-atomic resolution 3D structures of biological macromolecules. To meet the increasing demand for cryoEM, automated methods that improve throughput and efficiency of microscope operation are needed. Currently, the targeting algorithms provided by most data-collection software require time-consuming manual tuning of parameters for each grid, and, in some cases, operators must select targets completely manually. However, the development of fully automated targeting algorithms is non-trivial, because images often have low signal-to-noise ratios and optimal targeting strategies depend on a range of experimental parameters and macromolecule behaviors that vary between projects and collection sessions. To address this, Ptolemy provides a pipeline to automate low- and medium-magnification targeting using a suite of purpose-built computer vision and machine-learning algorithms, including mixture models, convolutional neural networks and U-Nets. Learned models in this pipeline are trained on a large set of images from real-world cryoEM data-collection sessions, labeled with locations selected by human operators. These models accurately detect and classify regions of interest in low- and medium-magnification images, and generalize to unseen sessions, as well as to images collected on different microscopes at another facility. This open-source, modular pipeline can be integrated with existing microscope control software to enable automation of cryoEM data collection and can serve as a foundation for future cryoEM automation software.
A call for impact! Launch of the new impact article
Authors: Keeling Debbie Isobel , Marshall Greg W.
Published: November 2022

Purpose

The research landscape is rapidly changing and people need to evolve the way in which they think about publishing their work. The purpose of this paper is to introduce the new article type – the impact article – which is specifically designed to allow collaborators to showcase their impact work and also share learning about how impact is (or is not) achieved.

Design/methodology/approach

This introductory paper outlines the rationale for the impact article and explains its new structure, using examples from the very first set of five impact articles to be published in the journal.

Findings

There is a clear appetite for sharing and learning more about the reality of impact. Providing a facilitating structure to enable sharing, this study identifies five core building blocks to bringing about valuable impact: problem generation and identifying the impact to be achieved; working with stakeholders; the (co-)creation and learning process; impact outcomes; and the ethics of impact.

Research limitations/implications

The new impact article type encourages authors to explore the impact process from start to finish, and to share learning about the process, including dealing with the unexpected and often changing nature of impact. These important learnings will inform future impact work, especially learning about what can (and cannot) be achieved and in what timeframes.

Practical implications

Collaboration is key to achieving impact. The new impact article aims to give voice to all stakeholders, through co-authorship opportunities and exploring the differences in perspectives on impact between stakeholders, including differing understanding of the ethics of impact. And to encourage multi-stakeholder co-creative working by enabling the sharing of best practice models and methods of collaborative working.

Originality/value

This new type of article aims to celebrate and make explicit the impact of research and so complements existing types of articles that might be separately published on the research itself. The impact article is designed to facilitate knowledge exchange about impact, not underlying research conceptualization and methodologies, but the challenge of designing, developing, tracking and demonstrating impact.
Making sense of internal social media and participatory communication: exploring the employee perspective in a change process in a public sector organization
Authors: Madsen Vibeke Thøis
Published: November 2022

Purpose

This article explores how employees in a public sector organization (PSO) make sense of the introduction of a social intranet and new employee communication roles. The aim is to understand employee sensemaking and how sensemaking influences the change process within the organization.

Design/methodology/approach

The article is based on a case study in a Danish PSO with 30,000 employees. The empirical material includes strategic documents, online observations and seven focus groups with employees conducted before, during and after the introduction of a new social intranet.

Findings

The employees found that making sense of the purpose with the social intranet is difficult. A managerial approach to change communication could easily result in employees' frustrations and concerns being dismissed as signs of resistance to change. From a communication perspective, the findings reveal that the employees engaged in seven different sensemaking enactments.

Research limitations/implications

Change cannot be understood simply as something that employees are for or against. Instead, a change process should be perceived as a set of communication processes or sensemaking enactments happening in interactions between employees that can act in favor of, against or neutrally toward change.

Practical implications

Managers and communication professionals can interact with the seven sensemaking enactments, and some tentative initiatives are suggested in the article.

Originality/value

The article explores the employee perspective in a change process in a PSO and identifies seven employee sensemaking enactments highlighting that change happens in communication processes.
Comparative study of drinking water management in Mexico City and Singapore
Authors: Silva Jorge Alejandro , Martínez Omaña María Concepción
Published: November 2022

Purpose

The aim of this research is to analyse the literature on drinking water management in Mexico City and Singapore, considering water supply, institutional organisation and management, and rates so as to propose recommendations for improvement in the water management of the Mexico City.

Design/methodology/approach

The preferred reporting items for systematic reviews and meta-analysis (PRISMA) methodology is used to review the literature on drinking water management in Mexico City and Singapore in time periods from 1325 to 2021 and from 1819 to 2021, respectively, emphasising the contemporary part. The information search was realised through different prestigious databases and official documents from the governments of Mexico and Singapore, as well as international organisations. After analysing, 40 documents were included to discuss the results.

Findings

There is a contrast between water management in Singapore and Mexico City because Singapore has strong institutions coordinated with each other along with the private and social sectors and has efficient fundraising and infrastructure investment systems. Although they are cities that developed in different circumstances, a comparison between them allowed to glimpse some aspects that may be useful to replicate in Mexico City.

Originality/value

This research is novel because there is no comparative analysis like the one presented in the literature, so it is suggested to continue delving into the topics covered in future research to have more elements that allow improving drinking water management in Mexico City.
Virtual-point-based geometric error compensation model for additive manufacturing machines
Authors: Zapico Pablo , Peña Fernando , Valiño Gonzalo , Rico José Carlos , Meana Víctor , Mateos Sabino
Published: November 2022

Purpose

The lack of geometric and dimensional accuracy of parts produced by additive manufacturing (AM) is directly related to the machine, material and process used. This paper aims to propose a method for the analysis and compensation of machine-related geometric errors applicable to any AM machine, regardless of the manufacturing process and technology used.

Design/methodology/approach

For this purpose, an error calculation model inspired by those used in computerized numerical control machines and coordinate measuring machines was developed. The error functions of the model were determined from the position deviations of a set of virtual points that are not sensitive to material and process errors. These points were obtained from the measurement of an ad hoc designed and manufactured master artefact. To validate the model, off-line compensation was applied to both the original designed artefact and an example part.

Findings

The geometric deviations in both cases were significantly smaller than those found before applying the geometric compensation. Dimensional enhancements were also achieved on the example part by using a correction parameter available in the three-dimensional printing software, whose value was adjusted from the measurement of the geometrically compensated master artefact.

Research limitations/implications

The errors that persist in the part derive from both material and process. Compensation for these type of errors requires a detailed analysis of the influencing parameters, which will be the subject of future research.

Originality/value

The use of the virtual-point-based error model increases the quality of additively manufactured parts and can be used in any AM system.
Tour guides’ sustainable tourism practices in host-guest interactions: when Tibet meets the west
Authors: Pu Pian , Cheng Li , Samarathunga WHMS , Wall Geoffrey
Published: November 2022

Purpose

Tour guides play a significant role in sustainable tourism development as leaders, mediators, resource managers and promoters of economic prosperity. This paper aims to show how local Tibetan tour guides practice sustainable tourism in their encounters with Western tourists.

Design/methodology/approach

The data consists primarily of 15 in-depth interviews with native Tibetan guides,Content analysis of the data were undertaken.

Findings

It was found that the guides adopt sustainable tourism practices based on their local religious wisdom and experiences as they try to establish harmonious host–guest relationships. Western clients also encourage guides to adopt more proenvironmental behaviors. The “hosts” live by Buddhist concepts such as samsara that are in line with concepts such as altruism and benevolence. Most “guests” are well-behaved and try to build sincere mutual relationships with local people. Host and guest cocreate value for local sustainable tourism practice.

Practical implications

Tour guides can practice sustainable tourism in a leadership role or as mediators, resource managers or promoters of economic prosperity. They also maintain a sincere and kind relationship with their guests that goes beyond the instrumental host–guest relationship and might help to cocreate value for local sustainable tourism practices.

Originality/value

Tour guides’ sustainable practices have been examined in the past based on their roles as leader, mediator, resource manager and promoter of economic prosperity. But researchers have seldom examined circumstances in which the tourists and tour guides were from different cultures. This paper addresses this gap.
Cardioprotective potential of vanillic acid
Authors: Yalameha Banafsheh , Nejabati Hamid Reza , Nouri Mohammad
Published: November 2022

Nowadays, cardiovascular diseases (CVDs) are a global threat to public health, accounting for almost one‐third of all deaths worldwide. One of the key mechanistic pathways contributing to the development of CVDs, including cardiotoxicity (CTX) and myocardial ischaemia–reperfusion injury (MIRI) is oxidative stress (OS). Increased generation of reactive oxygen species (ROS) is closely associated with decreased antioxidant capacity and mitochondrial dysfunction. Currently, despite the availability of modern pharmaceuticals, dietary‐derived antioxidants are becoming more popular in developed societies to delay the progression of CVDs. One of the antioxidants derived from herbs, fruits, whole grains, juices, beers, and wines is vanillic acid (VA), which, as a phenolic compound, possesses different therapeutic properties, including cardioprotective. Based on experimental evidence, VA improves mitochondrial function as a result of the reduction in ROS production, aggravates antioxidative status, scavenges free radicals, and reduces levels of lipid peroxidation, thereby decreasing cardiac dysfunction, in particular CTX and MIRI. Considering the role of OS in the pathophysiology of CVDs, the purpose of this study is to comprehensively address recent evidence on the antioxidant importance of VA in the cardiovascular system.
Legal Protection Against Destitution in the UK: the Case for a Right to a Subsistence Minimum
Authors: Simpson Mark , McKeever Gráinne , Fitzpatrick Ciara
Published: November 2022

In a 2003 Supreme Court judgment, Lord Hoffmann argued that in the absence of a guaranteed minimum standard of living, many other rights are reduced to ‘a mockery’. Given research findings that 2.4 million UK residents experienced destitution in 2019, this article considers whether a social floor exists in law and the implications of its absence or weakness for the standard of human rights protection in the UK. The common law, social rights treaties and the European Convention on Human Rights can each play a role in identifying a minimum standard of living, but with variable precision, generosity and enforceability – and subject to the sovereign legislature setting its own social floor, including one that may render people destitute. With an analysis of the case law revealing clear weaknesses in protection against destitution, the authors argue that a specific statutory duty is required to address this failure of rights protection.
Metabolic profile determination of 2F‐viminol – A novel synthetic opioid identified in forensic investigations
Authors: Velez Aracelis , Papsun Donna M. , Scott Karen S. , Krotulski Alex J.
Published: November 2022

Novel synthetic opioid (NSO) continue to emerge in the United States in the midst of an opioid crisis. The NSO 2F‐viminol was identified in casework at the Center for Forensic Science Research and Education through its NPS Discovery program in 2019. Little information and published literature were available for this new opioid at the time. To address this, human liver microsomes (HLMs) were used to perform in vitro metabolism studies with a drug standard. The goal was to predict in vivo metabolism. Experimental samples were prepared using HLMs, NADPH, phosphate buffer (pH 7.4), and a 2F‐viminol standard. Standard samples were prepared containing only drug, control samples were prepared with drug and HLMs but no NADPH cofactor, and metabolism reaction mixtures contained drug, HLMs and NADPH. The subsequent mixtures were incubated with light shaking to allow metabolism to occur. After cleanup, metabolite mixtures were analyzed via a SCIEX TripleTOF 5600+ liquid chromatograph quadrupole‐time‐of‐flight mass spectrometer (LC‐QTOF‐MS). The generated metabolic structures were elucidated using SCIEX MetabolitePilot software (version 2.0). In addition to remaining parent drug, seven metabolites of 2F‐viminol were discovered, including N‐dealkylated and hydroxylated species. The proposed primary metabolites of 2F‐viminol were N‐dealkylation (sec‐butyl) + hydroxylation and N‐dealkylation (sec‐butyl); however, they should be confirmed in authentic samples, and forensic laboratories should consider adding 2F‐viminol and its metabolites to screening protocols to help in extending the window of detection for the parent drug in toxicological samples. As NSOs continue to appear, forensic laboratories must continue metabolism experiments to generate information about pharmacokinetics.
Potential distribution of the silver stripped skipper (Leptalina unicolor) and maiden silvergrass (Miscanthus sinensis) under climate change in South Korea
Authors: Adhikari Pradeep , Kim Hyun Woo , Shin Man‐Seok , Hong Sun Hee , Cho Youngho
Published: November 2022

Globally, changes in the climate and in land cover are the most prominent factors affecting the distribution of flora and fauna, including butterflies. Therefore, this study was designed to assess the impact of climate and land cover changes on the potential habitat of the endangered butterfly Leptalina unicolor and its principal host, Miscanthus sinensis, in South Korea. We developed a species distribution model using the maximum entropy modeling approach and evaluated the current and future potential distributions of both species. Currently, the potential habitat of L. unicolor is predicted to be located along the Baekdudaegan mountain range and some isolated patches of its western and southern regions, covering an area of approximately 16,865 km2. However, due to future climate change, its potential habitat would decrease on a large scale (by up to 80.39%), thus limiting its existence to the northeastern region. On the other hand, the host plant (M. sinensis) was estimated to live in all parts of the country under both current and future climate conditions, covering up to 50.45% of the country. Our results showed that future climate and land cover changes will critically reduce the habitat of L. unicolor and limit its existence to relatively cold areas. This study suggests that, in addition to the host habitat, climate and land cover changes also play important roles in the future distribution of L. unicolor. This study predicted the current and future potential habitats of L. unicolor and M. sinensis to help develop management policies for the conservation of this endangered butterfly in South Korea.
Paleo‐ to Mesoproterozoic Tectono‐Magmatic Events Recorded in the Huwan Complex from the Dabie Orogen, Central China: Evidence from Petrology and U‐Pb Geochronology
Authors: ZHU Jiang , CHEN Yuqiong , CHEN Chao , LI Zhanke , SHI Xianbin , CHEN Song , ZOU Yuanbing
Published: November 2022

To better understand the Paleo‐ to Mesoproterozoic tectonic evolution of the Dabie Orogen in the northern margin of Yangtze Block, we present geochronological data for metasedimentary and metavolcanic rocks in the Huwan complex. A total of 385 detrital zircon LA‐ICP‐MS analyses for metasedimentary rocks yielded three207Pb/206Pb age populations: 1.50–1.80 Ga, 1.81–1.87 Ga and 1.93–2.0 Ga, providing a maximum depositional timing of ca. 1.50 Ga; while metafelsic volcanic gneisses yielded protolith U‐Pb ages of 1893 ± 54 Ma. The peak ages are remarkably consistent with the tectonothermal events that occurred in the northern Yangtze Block, indicating the presence of Paleo‐ to Mesoproterozoic magmatism in the Dabie Orogen. The age range of 1.93–2.0 Ga correlates with the Paleoproterozoic collision; the age range of 1.81–1.87 Ga coincides with the period of the post‐orogenic extension; and the age range of 1.50–1.80 Ga is interpreted to associate with an extensional regime. Zircon cores with age of 1732–1965 Ma haveεHf(t) values ranging from –11.70 to –2.47, indicating that juvenile crust involved in their magma sources. Owing to the similar age spectra, we proposed that the nucleus of the Dabie Orogen was close to the Yangtze Block since the Paleoproterozoic. The Huwan complex has an intimate affiliation to the Yangtze Block, and implies multiple orogenic cycles. It was not only experienced the Paleo‐Tethys ocean subduction and collision, but also recorded Paleo‐ to Mesoproterozoic tectono‐magmatic events in the Dabie Orogen.
The organisational dimension of executive authority in the Global South: Insights from the AU and ECOWAS commissions
Authors: Trondal Jarle , Tieku Thomas , Gänzle Stefan
Published: November 2022

The growing importance of executive authority at the international level has fuelled scholarly debate about the level of autonomy enjoyed by international public administration (IPA), that is, the executive arms of international organisations. Insights from IPAs in the West or Global North, such as the European Union, have largely shaped these debates, whereas data from IPAs in the Global South are largely missing in the discussion. This article seeks to remedy this imbalance and contribute to an organisational‐theory‐inspired conceptualisation of IPA autonomy: We draw insights from survey data from the commissions of the African Union (AU) and the Economic Community of West African States (ECOWAS). We demonstrate that, although both commissions are embedded in inter‐governmental organisations, they demonstrate remarkably strong features of actor‐level autonomy. Thus, this study suggests that even IPAs constrained by an inter‐governmental environment may still wield some degree of autonomy. Finally, the article draws practical implications for reforming IPAs.
Surgical management of breast cancer in Victoria: A state‐wide audit
Authors: Sung Nakjun , Muthusamy Arun , Finn Norah , Stuart Ella , Fox Jane , Yeo Belinda
Published: November 2022

Aim

The Victorian Tumour Summits are an initiative of the Victorian Integrated Cancer Services to engage clinicians and consumers in identifying unwarranted variations in cancer care across the state. From the analysis presented at the Victorian Breast Tumour Summit in 2021, this study provides a state‐wide overview of epidemiology and surgical care of breast cancer in Victoria to outline any variations in care across the state, and limitations in data reporting, which impacts the understanding of breast cancer burden and service planning.

Methods

A retrospective analysis of Victorian breast cancer patients diagnosed between 2016 and 2018 was performed using a linked data set provided by the Department of Health. The linked data sources include Victorian Cancer Registry, Victorian Admitted Episodes Dataset and Victorian Radiotherapy Minimum Data Set, from which patient demographic details, tumor characteristics and treatment records were extracted. Pearson's chi‐squared test was used to determine the statistical significance of relationships between various categorical parameters. Variables including demographics, types of surgery (breast‐conserving vs. mastectomy), rates of neoadjuvant chemotherapy, and time to surgery were examined.

Results

One thousand nine hundred thirty‐seven patients with ductal carcinoma in situ and 13,375 patients with invasive breast cancer (IBC) were included. Of 11,351 patients with stages I‐III IBC (85%, N = 13,375) 66% underwent breast‐conserving surgery (BCS), and 31% underwent mastectomy. The ratio of mastectomy to BCS increased with increasing disease stage. Neoadjuvant chemotherapy was utilized in 11% of early IBC patients who were surgically treated. Eighty‐three percent of patients undergoing upfront breast surgery were treated within 5 weeks of diagnosis, with a significant difference in the median time to surgery between public and private sectors. Breast reconstruction was performed in 37% of mastectomy patients, of whom 83% underwent immediate breast reconstruction, and 17% underwent delayed breast reconstruction.

Conclusions

Victorian breast cancer data show a high quality of surgical care coordination. Significant gaps in our data warrant future improvements in the Victorian breast cancer notification system and access to pharmaceutical data for an enhanced understanding of the breast cancer treatment pathways and care delivery.
Specialist pharmacist consultations with cancer patients in a pharmacist‐led anticancer clinic
Authors: Soggee Johnathan , Hunt Maddaleine , O'Callaghan Barbara , Lam Wei‐Sen , Cannell Paul , Boardman Glenn , Sunderland Bruce , Czarniak Petra
Published: November 2022

Background

Prescription‐related errors and misinterpretation of oral cancer treatment instructions can lead to significant harm or fatal outcomes for patients. The impact of specialist pharmacist‐led consultation for patients taking oral antineoplastic medicines (OAMs) across a range of cancer types in an Australian setting has not been studied.

Aim

To evaluate the impact of specialist cancer pharmacist patient consultation in a pharmacist‐led anticancer clinic across a range of cancer types and evaluate health service staff perceptions of these consultations.

Method

Retrospective data were collected from electronic patient medical records from 2017 to 2020 at a Western Australian quaternary hospital. The impacts of pharmacist clinical interventions were classified using a validated tool and specialist interdisciplinary panel consensus. An online staff survey was conducted using Qualtrics.

Results

Of 246 patients reviewed, 76 (30.8%, p < .001) had received a clinical intervention of which 48 (63.2%) were classified as high‐extreme and 28 (36.8%) as low‐moderate impact (p = .021). Patients on ≥5 concurrent medications or > 65 years may represent high risk groups. Thirty‐seven clinical staff were surveyed (37/55; 67.3%) and all strongly agreed/ agreed pharmacist consultation improved patient understanding and medication management confidence (p < .001). All cancer center staff (26/26) strongly agreed/agreed the clinic added value to the cancer service (p < .001), and 96.2% perceived it improved patient outcomes (p < .001).

Conclusions

Specialist pharmacist‐led patient consultation for patients on OAM regimens may protect patients from high and extreme risk of harm. Specialist interdisciplinary staff supported this service.
Use of 3D anatomical models in mock circulatory loops for cardiac medical device testing
Authors: Rocchi Maria , Ingram Marcus , Claus Piet , D'hooge Jan , Meyns Bart , Fresiello Libera
Published: November 2022

Introduction

Mock circulatory loops (MCLs) are mechanical representations of the cardiovascular system largely used to test the hemodynamic performance of cardiovascular medical devices (MD). Thanks to 3 dimensional (3D) printing technologies, MCLs can nowadays also incorporate anatomical models so to offer enhanced testing capabilities. The aim of this review is to provide an overview on MCLs and to discuss the recent developments of 3D anatomical models for cardiovascular MD testing.

Methods

The review first analyses the different techniques to develop 3D anatomical models, in both rigid and compliant materials. In the second section, the state of the art of MCLs with 3D models is discussed, along with the testing of different MDs: implantable blood pumps, heart valves, and imaging techniques. For each class of MD, the MCL is analyzed in terms of: the cardiovascular model embedded, the 3D model implemented (the anatomy represented, the material used, and the activation method), and the testing applications.

Discussions and Conclusions

MCLs serve the purpose of testing cardiovascular MDs in different (patho‐)physiological scenarios. The addition of 3D anatomical models enables more realistic connections of the MD with the implantation site and enhances the testing capabilities of the MCL. Current attempts focus on the development of personalized MCLs to test MDs in patient‐specific hemodynamic and anatomical scenarios. The main limitation of MCLs is the impossibility to assess the impact of a MD in the long‐term and at a biological level, for which animal experiments are still needed.
Review article: the safety of anticoagulants and antiplatelet agents in patients with cirrhosis
Authors: Ma Jiayi , Chalasani Naga P. , Schwantes‐An Linus , Björnsson Einar Stefán
Published: November 2022

Patients with cirrhosis were long thought to be coagulopathic. However, this paradigm has changed in recent years and currently, cirrhosis is recognised as a prothrombotic state. Due to the increasing incidence of cirrhosis from nonalcoholic steatohepatitis which is closely associated with cardiac disease, patients with cirrhosis increasingly require therapy with anticoagulants and antiplatelet agents. However, their potential for causing catastrophic and life‐threatening bleeding in patients with cirrhosis leads to hesitancy about their use in patients with cirrhosis. Overall, traditional anticoagulation is safe for all Child‐Pugh classes while newer direct oral anticoagulants (DOACs) are mostly safe in Child‐Pugh class A/B and contraindicated in severe hepatic impairment. For different indications, published data to date suggest that anticoagulation is overall safe for patients with cirrhosis who have venous thromboembolism, atrial fibrillation and portal vein thrombosis, and does not increase the risk of variceal bleeding. Moreover, DOACs appear to have similar safety profiles as traditional anticoagulants. Finally, most studies suggest that antiplatelet agents are also safe to use in patients with cirrhosis although they are mostly contraindicated in severe hepatic impairment. For both anticoagulants and antiplatelet agents, severe thrombocytopaenia presents a relative contraindication to their use. More prospective trials and large cohort studies are needed to advance our understanding of the safety and nuances of DOACs and antiplatelet agents in patients with advanced cirrhosis.
Randomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndrome
Authors: Quigley Eamonn M. M. , Markinson Louise , Stevenson Alex , Treasure F. Peter , Lacy Brian E.
Published: November 2022

Background

MRx1234 is a live biotherapeutic product that contains a strain of Blautia hydrogenotrophica. It is in development for the treatment of irritable bowel syndrome (IBS).

Aims

To assess the efficacy and safety of MRx1234 in patients with IBS with predominant constipation (IBS‐C) or diarrhoea (IBS‐D)

Methods

We conducted a multicentre, randomised, double‐blind, placebo‐controlled, phase 2 trial. Patients aged 18–70 years in two parallel cohorts (IBS‐C; IBS‐D) were randomised (1:1) to MRx1234 or placebo for 8 weeks. The primary efficacy endpoint was overall responder rate—a composite of improved bowel habit (IBS‐C: stool frequency; IBS‐D: stool consistency) and abdominal pain intensity—for ≥50% of the treatment period in each cohort. Statistical testing was at a one‐sided 0.10 significance level.

Results

Of 366 randomised patients (164 IBS‐C; 202 IBS‐D), 365 received any study medication (177 MRx1234, 188 placebo). Numerically, although not statistically significantly different, more patients who received MRx1234 than placebo were overall responders in the IBS‐C (25.0% vs. 17.1%) and IBS‐D (23.4% vs. 17.8%) cohorts. Similar results were observed in the additional combined cohort analysis (24.1% vs. 17.5%; p = 0.063). For the components of the primary endpoint, significantly more patients on MRx1234 than placebo reported improvement in bowel habit in the IBS‐C, IBS‐D and combined cohorts, while improvements in abdominal pain were observed in each cohort. The safety profile of MRx1234 was similar to placebo.

Conclusions

MRx1234 has the potential to become a novel, safe treatment option for patients with IBS‐C or IBS‐D, and for those who have mixed symptoms or transition between subtypes.

ClinicalTrials.gov #NCT03721107.
Management of acquired haemophilia A in severe Covid‐19: Haemostatic bridging with emicizumab to keep the balance between bleeding and thrombosis
Authors: Gelbenegger Georg , Traby Ludwig , Rahimi Nina , Knöbl Paul
Published: November 2022

Acquired haemophilia A (AHA) is an autoimmune bleeding disorder caused by autoantibodies blocking coagulation factor VIII (FVIII). Haemostatic management of AHA and concomitant thrombotic risk is difficult. We cover the management of a 75‐year‐old male with severe Covid‐19, a prothrombotic disease, and de novo AHA with severe muscle bleeding, a disease requiring highly thrombogenic haemostatic therapy and immunosuppression—a challenging combination. FVIII activity was measured using human and bovine reagents to differentiate between endo‐ and exogenous FVIII activity. For haemostatic control, recombinant human activated FVII was given, followed by emicizumab, as a less thrombogenic long‐term haemostatic agent. Steroids were used as initial immunosuppressive therapy. Later, rituximab was used for inhibitor eradication. No thromboembolic events occurred, and bleeding was effectively controlled. Emicizumab achieved haemostatic balance in a patient under haemorrhagic and thrombogenic conditions. Individual risk assessment is needed to guide treatment decisions in patients threatened by simultaneous bleeding and thrombosis.
Effects of chronic cirrhosis induced by intraperitoneal thioacetamide injection on the protein content and Michaelis–Menten kinetics of cytochrome P450 enzymes in the rat liver microsomes
Authors: Chandrashekar Devaraj Venkatapura , DuBois Barent N. , Rashid Mamunur , Mehvar Reza
Published: November 2022

Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10‐day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O‐deethylase activity, a general marker of P450 activity, were significantly reduced by 30%–50% in cirrhotic animals. Additionally, the protein content and Michaelis–Menten kinetics of the activities of CYP2D, CYP2E1 and CYP3A were investigated. Whereas cirrhosis reduced the microsomal protein contents of CYP2D and CYP3A by 70% and 30%, respectively, the protein contents of CYP2E1 were not affected. However, the activities of all the tested isoenzymes were substantially lower in the cirrhotic livers. It is concluded that the TAA model of cirrhosis that incorporates a 10‐day washout period after intraperitoneal injection of the chemical to rats produces isoenzyme‐selective reductions in the P450 proteins or activities, which are independent of the direct inhibitory effects of TAA.
How do central banks make decisions?
Authors: Ruge‐Murcia Francisco
Published: November 2022

This paper studies decision making by the governing council of the Bank of Canada under two alternative protocols. The protocols are: (i) the median model and (ii) the inclusive‐voting model due to Riboni and Ruge‐Murcia (2020), where the chair and the median share proposal power. Results show that the data favour a version of the inclusive‐voting model where the chair of the committee is moderately inclusive and which endogenously generates the consensus outcome in Riboni and Ruge‐Murcia (2010). Decision‐making frictions are empirically important in the formulation of monetary policy, and the selected policy is the outcome of a compromise between committee members.
The perilous prerogative: An argument for legislating defence intelligence in Canada
Authors: West Leah
Published: November 2022

The National Security and Intelligence Committee of Parliamentarians (NSICOP) has twice reviewed the intelligence activities of CAF/DND and recommended the government provide explicit legislative authority for those activities. In “Defence intelligence and the Crown prerogative in Canada,” Philippe Lagassé rebukes NSICOP's argument and defends the continued reliance on the Crown prerogative. This article proposes that the critiques raised by Lagassé minimize the importance of the legal and operational concerns raised by NSICOP and do not reflect the legal history of Canadian intelligence activities. It also introduces the argument that the DND/CAF may no longer rely on the Crown prerogative for signals intelligence.
Clinicopathological features and prognostic impact of dirty necrosis in metastatic lung cancers from the colon and rectum
Authors: Konishi Yasuhito , Taki Tetsuro , Nakai Tokiko , Kuroe Takashi , Morisue Ryo , Miyoshi Tomohiro , Tane Kenta , Samejima Joji , Aokage Keiju , Miyazaki Saori , Sakamoto Naoya , Sakashita Shingo , Watanabe Reiko , Kojima Motohiro , Suzuki Kenji , Tsuboi Masahiro , Ishii Genichiro
Published: November 2022

Dirty necrosis (DN) is a form of tumor necrosis (TN) with prominent neutrophil infiltration and cell detritus in the necrotic foci. This study aimed to characterize the clinicopathological features of DN in metastatic lung cancers of the colon and rectum (MLCRs). A total of 227 patients who underwent pulmonary metastasectomy and complete resection for MLCR were included in this study. TN was evaluated using digitally scanned resection specimens. These slides were immunostained for biomarkers of NETosis (citrullinated histone H3 [citH3] and myeloperoxidase [MPO]), and the area positive for citH3 and MPO was further quantified. TN was observed in 216 cases (95.2%), and 54 (25.0%) of these cases had DN. The presence of TN was not associated with a worse prognosis; however, patients with DN had a significantly shorter overall survival than those without DN (p < 0.01). Furthermore, the presence of DN was a poor prognostic factor in both the univariate and multivariate analyses. Immunohistochemical analysis revealed that the percentage of citH3‐positive and MPO‐positive areas in the DN‐positive cases was significantly higher than that in the DN‐negative cases (p < 0.01 and p < 0.01, respectively). In surgically resected MLCR, DN is the characteristic TN subtype associated with poor prognosis and neutrophil extracellular traps (NETs).
Shikonin reverses pyruvate kinase isoform M2‐mediated propranolol resistance in infantile hemangioma through reactive oxygen species‐induced autophagic dysfunction
Authors: Yang Enli , Wang Xuan , Huang Shengyun , Li Mingyang , Li Yiming , Geng Yiming , Liu Xuejian , Chen Zhanwei , Zhang Dongsheng , Wu Haiwei
Published: November 2022

Infantile hemangioma (IH) is the most common benign tumor in infancy. Propranolol, a nonselective β‐adrenergic receptor blocker, is now the first‐line therapy for IH. Recently, low sensitivity to propranolol therapy has become one major reason for the failure of IH treatment. However, the exact underlying mechanisms are yet to be fully elucidated. Here, we reported that pyruvate kinase isoform M2 (PKM2), an essential glycolytic enzyme, played a critical role in regulating the progression of IH and the therapeutic resistance of propranolol treatment. Shikonin reversed the propranolol resistance in hemangioma‐derived endothelial cells and in hemangioma animal models. Moreover, shikonin combined with propranolol could induce excessive reactive oxygen species (ROS) accumulation and lead to autophagic dysfunction, which is essential for the enhanced therapeutic sensitivity of propranolol treatment. Taken together, our results indicated that PKM2 has a significant role in hemangiomas progression and therapeutic resistance; it could be a safe and effective therapeutic strategy for those hemangiomas with poor propranolol sensitivity combined with shikonin.
Clinical, radiographic, and esthetic evaluation of immediate implant placement with buccal bone dehiscence in the anterior maxilla: A 1‐year prospective case series
Authors: Qian Shu‐Jiao , Pu Yi‐ping , Zhang Xiao‐Meng , Wu Xin‐yu , Liu Bei‐lei , Lai Hong‐Chang , Shi Jun‐Yu
Published: November 2022

Objectives

To evaluate the clinical, radiographic, and esthetic outcomes of immediate implant placement with buccal bone dehiscence in the anterior maxilla.

Methods

In this case series, implants were inserted immediately after tooth extraction in sockets with buccal bone dehiscence. Guided bone regeneration (GBR) with a papilla preservation flap and simultaneous connective tissue grafting (CTG) was used. The following outcome variables were measured: mid‐facial mucosal recession, probing depth, bleeding on probing, Pink Esthetic Score (PES), marginal bone loss, and thickness of buccal bone plate (TBP).

Results

12 patients were recruited. Stable mid‐facial mucosal level (−0.03 ± 0.17 mm) and excellent soft‐tissue esthetic outcomes (PES, 9.17 ± 0.72) were achieved at 1 year. The TBP at platform level was 2.01 ± 0.31 mm at 1‐year follow up with a resorption rate of 28.90% ± 15.14%.

Conclusions

Immediate implant placement using GBR performed with a papilla preservation approach and simultaneous CTG is a feasible treatment procedure in compromised extraction sockets in the anterior region. Favorable esthetic outcomes and buccal bone thickness were obtained. Further studies were needed to evaluate the long‐term tissue alteration.
Findings from the British Childhood Visual Impairment and Blindness Study 2: Implications for children in low‐income countries
Authors: Le Fanu Guy
Published: November 2022

This commentary is on the original article by Solebo et al. on pages 803–810 of this issue.
DSJIE: Reflections on the past and a look to the future
Authors: Kannan Vijay R.
Published: November 2022

As the Decision Sciences Journal of Innovative Education embarks on its third decade, a former editor reflects on the first two decades and offers thoughts on the future of the journal and decision sciences education.
The early Christian origins of voluntary poor relief
Authors: Koehler Benedikt
Published: November 2022

Poor relief funded by voluntary contributions originated in early Christianity. Roman paganism did not practise poor relief; post‐exilic Judaism practised poor relief funded by mandatory contributions; early Christianity introduced poor relief on a voluntary basis. Jesus, Peter, and Paul were formative for early Christian poor relief. Jesus set examples of dispensing alms and respecting private property. Peter and Paul agreed on the duty to fund poor relief but did not agree whether funding of poor relief was mandatory or voluntary. The variant approaches of Peter and Paul to how to reconcile poor relief with property rights opened a fault line that has persisted throughout Christian history.
Comparison of outcomes between Hodgkin's lymphoma patients treated in and outside clinical trials: A study based on theEORTC‐Dutchlate effects cohort‐linked data
Authors: Juul Sidsel Jacobsen , Kicinski Michal , Schaapveld Michael , Rossetti Sára , Aleman Berthe M. P. , Liu Lifang , van Leeuwen Flora E. , Meijnders Paul , Krol Augustinus D. G. , Janus Cécile P. M. , Hutchings Martin , Maraldo Maja V.
Published: November 2022

Studies have shown higher survival rates for patients with Hodgkin lymphoma (HL) treated within clinical trials compared to patients treated outside clinical trials. However, endpoints are often limited to overall survival (OS). In this retrospective cohort study, we investigated the effect of trial participation on OS, the incidence of relapse, second cancer, and cardiovascular disease (CVD). The study population consisted of patients with HL, aged between 14 and 51 years at diagnosis, who started their treatment between 1962 and 2002 at three Dutch cancer centres. Patients were either included in the EORTC Lymphoma Group trials (H1–H9) or treated according to standard guidelines at the time. After adjusting for differences in baseline characteristics, trial participation was associated with longer OS (median OS: 29.4 years [95%CI: 27.0–31.6] for treatment inside trials versus 27.4 years [95%CI: 26.0–28.5] for treatment outside trials,p = .046), a lower incidence of relapse (HR = 0.79, 95%CI: 0.63–0.98,p = .036) and a higher incidence of CVD (HR = 1.49, 95%CI: 1.23–1.79,p < .001). The trial effect for CVD was present only for patients treated before 1983. No evidence of differences in the incidence of second cancer was found. Consequently, essential results from clinical trials should be implemented into standard practice without undue delay.
Disruption of the anterior commissure in Olig2 deficient mice
Authors: Gotoh Hitoshi , Maruyama Kohei , Yoshii Kengo , Yamauchi Nao , Nomura Tadashi , Ohtsuka Satoshi , Shirasaki Ryuichi , Takebayashi Hirohide , Ono Katsuhiko
Published: November 2022

In the present study, we examined neural circuit formation in the forebrain of the Olig2 knockout (Olig2‐KO) mouse model and found disruption of the anterior commissure at the late foetal stage. Axon bundles of the anterior commissure encountered the wall of the third ventricle and ceased axonal extension. L1‐CAM immunohistochemistry showed that Olig2‐KO mice lose decussation formation in the basal forebrain. DiI tracing revealed that the thin bundles of the anterior commissure axons crossed the midline but ceased further extension into the deep part of the contralateral side. Furthermore, some fractions of DiI‐labelled axons were oriented dorsolaterally, which was not observed in the control mouse forebrain. The rostral part of the third ventricle was much wider in the Olig2‐KO mice than in wild‐type mice, which likely resulted in the delay of midline fusion and subsequent delay and malformation of the anterior commissure. We analysed gene expression alterations in the Olig2‐KO mice using a public database and found multiple genes, which are related to axon guidance and epithelial‐mesenchymal transition, showing subtle expression changes. These results suggest that Olig2 is essential for anterior commissure formation, likely by regulating multiple biological processes.
Public sector accounting harmonization in the European Union through the lens of the garbage can model
Authors: Cohen Sandra , Manes Rossi Francesca , Brusca Isabel
Published: November 2022

The public sector accounting harmonization process that started in the European Union in the aftermath of the financial crisis led the European Commission to launch a project for the development of a set of European Public Sector Accounting Standards (EPSAS). This paper analyses the process and the decision‐making around development of the EPSAS through the lens of thegarbage can model(Cohen, M. D., March, J. G., & Olsen, J. P. (1972). A garbage can model of organizational choice.Administrative Science Quarterly,17(1), 1–25). More specifically, by identifyingproblems,participants,solutions, andchoice opportunities, it discusses why the development of the EPSAS is taking so long and why the process does not seem to be progressing as planned. To this end, documents related to the process of EPSAS development are analyzed. The results provide evidence of problematic preferences and fluid participation possibly coupled with flight decisions—three elements of the garbage can model. Postponing decisions can be an option to dampen reluctance. The more the public sector becomes accustomed to the International Public Sector Accounting Standards (IPSAS) by adopting IPSAS‐like accrual accounting standards while waiting for the completion of the EPSAS, the less resistance there might be to moving to accrual accounting standards. However, at the same time, an imminent change to a new set of EPSAS standards might become less plausible if changes demand extra reform.
Effect of rafted microstructure and its temperature dependency on fatigue crack propagation in a single‐crystal Ni‐base superalloy
Authors: Sakaguchi Motoki , Okamoto Ryota , Karato Takanori , Suzuki Kenta
Published: November 2022

Effects of rafted microstructure and its temperature dependency on fatigue crack propagation (FCP) in a single‐crystal Ni‐base superalloy are experimentally investigated. FCP tests are conducted at room temperature, 450°C, and 700°C for two types of pre‐rafted specimens, and their FCP behaviors are compared with that of a specimen with cuboidal γ′ precipitates. It is found in the experiments that there is no significant influence of rafted microstructures on FCP rate at room temperature, while a clear influence is pronounced at 450 and 700°C depending on the coarsening direction of rafted microstructures and the level of stress intensity factor range. The temperature dependency in the effect of rafted microstructure is discussed with special considerations on the microscopic FCP behavior affected by the morphology of γ′ precipitates, the coherency of the γ/γ′ interface, and temperature‐dependent slip characteristics of γ and γ′ phases.