bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid liposome–erythrocyte drug delivery system for tumor therapy with enhanced targeting and blood circulation
Authors: Zhu Kehui , Xu Yingcan , Zhong Rui , Li Wanjing , Wang Hong , Wong Yee Shan , Venkatraman Subramanian , Liu Jiaxin , Cao Ye
Published: April 2023

Liposome, a widely used drug delivery system (DDS), still shows several disadvantages such as dominant clearance by liver and poor target organ deposition. To overcome the drawbacks of liposomes, we developed a novel red blood cell (RBC)–liposome combined DDS to modulate the tumor accumulation and extend the blood circulation life of the existing liposomal DDS. Here, RBCs, an ideal natural carrier DDS, were utilized to carry liposomes and avoid them undergo the fast clearance in the blood. In this study, liposomes could either absorbed onto RBCs’ surface or fuse with RBCs’ membrane by merely altering the interaction time at 37°C, while the interaction between liposome and RBCs would not affect RBCs’ characteristics. In the in vivo antitumor therapeutic efficacy study, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes attached onto RBCs’ surfaces exhibited lung targeting effect (via RBC-hitchhiking approach) and reduced clearance in the liver, while DPPC liposomes fused with RBCs had prolong blood circulation up to 48 h and no enrichment in any organ. Furthermore, 20 mol% of DPPC liposomes were replaced with pH-sensitive phospholipid 1,2-dioleoyl-Sn-glycero-3-phosphoethanolamine (DOPE) as it could respond to the low pH tumor microenvironment and then accumulate in the tumor. The DOPE attached/fusion RBCs showed partial enrichment in lung and about 5–8% tumor accumulation, which were significantly higher than (about 0.7%) the conventional liposomal DDS. Thus, RBC–liposome composite DDS is able to improve the liposomal tumor accumulation and blood circulation and shows the clinical application promises of using autologous RBCs for antitumor therapy.
lncRNA TUG1 regulates Smac/DIABLO expression by competitively inhibiting miR-29b and modulates the apoptosis of lens epithelial cells in age-related cataracts
Authors: Sun Miaomiao , Li Ke , Li Xiao , Wang Huajun , Li Li , Zheng Guangying
Published: April 2023

Background:

As one of the early discovered long non-coding RNAs (lncRNA), taurine upregulation gene 1 (TUG1) has been widely expressed in a variety of tumors. Moreover, it promotes cell proliferation, differentiation, apoptosis, and migration. However, our understanding of its importance in the pathogenesis of cataracts remains limited. This study aimed to explore the mechanism by which lncRNA TUG1 mediates lens epithelial cell apoptosis in age-related cataracts (ARC) by regulating the microRNAs (miR-29b)/second mitochondria-derived activator of caspases axis, and to identify more non-surgical strategies for cataract treatment.

Methods:

The messenger RNA expression levels of TUG1, miR-29b, and Smac were detected using quantitative real-time polymerase chain reaction in vivo and in vitro. The expression of the Smac protein was analyzed by Western blotting and immunofluorescence. Flow cytometry and cell counting kit-8 assays were used to detect the cell apoptosis and proliferation rates, respectively. The targeted regulatory relationship between lncRNA TUG1, miR-29b, and Smac was verified by viral vector construction, co-transfection, nuclear and cytoplasmic separation, luciferase reporter assays, and RNA immunoprecipitation.

Results:

TUG1 and Smac were expressed at high levels in ARC and HLE-B3 cells treated with 200 μmol/L H2O2, whereas miR-29b expression was decreased. In vitro cell experiments confirmed that down-regulation of TUG1 could inhibit the apoptosis of lens epithelial cells. Mechanistically, Smac expression was negatively regulated by miR-29b. TUG1 competitively inhibited miR-29b expression and caused greater release of Smac. In addition, miR-29b partially reversed the effects of TUG1 on human lens epithelial cell line cells.

Conclusions:

lncRNA TUG1 increases Smac expression and promotes apoptosis of lens epithelial cells in ARC by competitively inhibiting miR-29b. This mechanism is the cytological basis for ARC formation. Based on these results, the lncRNA TUG1/miR29b/Smac axis may be a new molecular pathway that regulates ARC development.
Machine and deep learning-based clinical characteristics and laboratory markers for the prediction of sarcopenia
Authors: Zhang He , Yin Mengting , Liu Qianhui , Ding Fei , Hou Lisha , Deng Yiping , Cui Tao , Han Yixian , Pang Weiguang , Ye Wenbin , Yue Jirong , He Yong
Published: April 2023

Background:

Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts.

Methods:

We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models.

Results:

The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC = 0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was RF (AUC = 0.892, ACC = 0.844), W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749).

Conclusions:

The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population.

Trial Registration:

Chictr.org, ChiCTR 1800018895.
Comparison of Visual Outcomes and Higher-order Aberrations Between FS-LASIK and SMI-LIKE for Moderate to High Hyperopia: A 2-Year Result
Authors: Lin Feng , Liu Shengtao , Fu Dan , Zhang Luoli , Wei Ruoyan , Li Meiyan , Zhou Xingtao
Published: April 2023

Purpose:

The aim of the study was to evaluate and compare the long-term visual outcomes and higher-order aberrations (HOAs) between femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small-incision lenticule intrastromal keratoplasty (SMI-LIKE) in the correction of moderate to high hyperopia.

Methods:

In this study, 16 subjects (20 eyes) underwent FS-LASIK and 7 subjects (10 eyes) underwent SMI-LIKE. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, mean keratometry (Km), anterior asphericity (Q), and HOAs preoperatively and 2 years postoperatively were obtained in both procedures.

Results:

The efficacy indices of the FS-LASIK group and the SMI-LIKE group were 0.85 ± 0.14 and 0.87 ± 0.17, respectively. The safety indices of the FS-LASIK and SMI-LIKE groups were 0.99 ± 0.15 and 1.08 ± 0.24, respectively. No significant difference in safety index or efficacy index was found between the FS-LASIK and SMI-LIKE groups (all P > 0.05). The correlation coefficient of the attempted versus achieved spherical equivalent postoperatively was 0.69 (P < 0.01) and 0.89 (P < 0.01) in the FS-LASIK group and SMI-LIKE groups, respectively. The front Km, negative Q value, negative spherical aberrations (SAs), coma, and total HOAs significantly increased postoperatively in the 2 groups (P < 0.05). The FS-LASIK group had greater changes in Q value and SA postoperatively than the SMI-LIKE group (P < 0.01).

Conclusions:

SMI-LIKE had similar safety and efficacy to FS-LASIK in the correction of moderate to high hyperopia. However, SMI-LIKE may equip better visual quality postoperatively for its lower Q value and SA changes than FS-LASIK.
Characterizing the Practices of Canadian Orthopedic Surgeons in the Management of patients With Anterior Glenohumeral Instability
Authors: Hemstock Riley , Sommer Micah , McRae Sheila , MacDonald Peter , Woodmass Jarret , Ogborn Dan
Published: April 2023

Objective:

To determine the practice patterns of Canadian orthopedic surgeons in the management of patients with anterior glenohumeral instability (AGHI).

Design:

Cross-sectional survey.

Setting:

Canada.

Patients or Other Participants:

Canadian orthopedic surgeons with membership in the Canadian Orthopedic Association or Canadian Shoulder and Elbow Surgeon group who had managed at least 1 patient with AGHI in the previous year.

Interventions:

A survey including demographics and questions on the management of patients with AGHI was completed. Statistical comparisons (χ2) were completed with responses stratified using the instability severity index score (ISIS) in practice, years of practice, and surgical volumes.

Main Outcome Measures:

Summary statistics were compiled, and response frequencies were considered for consensus (75%). Case series responses were stratified on use of the ISIS in practice, years of experience, and annual procedure volumes (χ2, P < 0.05).

Results:

Eighty orthopedic surgeons responded, with consensus on areas of diagnostic workup of AGHI, nonoperative management, and operative techniques. There was no consensus on indications for soft tissue and bony augmentation or postoperative management. There was no difference in practices based on the use of ISIS, years in practice, or surgical volumes.

Conclusions:

Canadian orthopedic surgeons manage AGHI consistently with consensus achieved in preoperative diagnostics and operative techniques, although debate remains as to the indications for soft tissue and bony augmentation procedures.
Leaders Are Readers Book Club to Enhance Interdisciplinary Hospital Leader Communication
Authors: Bethel Claire
Published: April 2023

Book clubs are a cost-effective strategy for professional development and to foster relationships. In 2022, hospital leaders at University of Pittsburgh Medical Center Community Osteopathic hospital created an interdisciplinary leadership book club. Communication, collaboration, and support among the leaders improved as a result.
Clustering drives cooperation on reputation networks, all else fixed
Authors: David-Barrett Tamas
Published: April 2023

Reputation-based cooperation on social networks offers a causal mechanism between graph properties and social trust. Using a simple model, this paper demonstrates the underlying mechanism in a way that is accessible to scientists not specializing in networks or mathematics. The paper shows that when the size and degree of the network is fixed (i.e. all graphs have the same number of agents, who all have the same number of connections), it is the clustering coefficient that drives differences in how cooperative social networks are.
The relationship between microbial community vitality and ATP bioburden in bottom waters under fuel microcosms
Authors: Passman Frederick Jay , Schmidt Jordan , Lewis Russell P.
Published: April 2023

Adenylate energy charge (AEC) – computed from the ATP, ADP and AMP concentrations in a specimen – reflect the net physiological state of the microbial population in that specimen. Previous research has demonstrated that healthy microbial populations maintain AEC≥0.8. As populations are subjected to stresses, or – in closed systems – deplete the available nutrients, respond to the accumulation of toxic metabolites, or both, AEC decreases (often to <0.5). Aqueous-phase samples from a set of fuel–water microcosms were tested for cellular ATP (cATP) and AEC. This paper reports on the precision of the AEC test method and the relationship between cellular AEC and cATP bioburdens in the aqueous phase of fuel over aqueous-phase microcosms.
A Quadrivalent mRNA immunization elicits potent immune responses against vaccinia and monkeypox viral antigens – a step closer to a broad orthopoxvirus vaccine
Authors: Su Caixia , Wen Yang , Geng Xiya , Yang Chunmei , Yin Quanyi , Xiong Yelin , Liu Zhihua
Published: April 2023

The global outbreak of the 2022 monkeypox virus infection of human raised the public health concerns of the threat of human-to-human transmission of zoonotic diseases. Given the evidence that other orthopoxviruses including cowpox and camelpox were also reported infectious to human, and that the reemerging risk of smallpox as a bioterrorist or accidental laboratory escape exists, there is an urgent need to develop a poxvirus vaccine with a broad protection of orthopoxviruses to stockpile for future emergency. Extensive studies of vaccinia virus (VACV) suggested that multiple VACV antigens, such as A27, L1, A33 and B5, showed high level similarity in terms of immunogenicity to their respective homologous antigens of other orthopoxviruses. These findings paved the ground for VACV antigens to be used as potential vaccine targets for development of a universal poxvirus vaccine. In this study, we construct a novel poxvirus vaccine candidate, mRNA-ALAB-LNP, encoding four vaccinia viral antigens A27, L1, A33 and B5. Strong anti-L1-specific antibody and moderate anti-A33-, anti-A27- and anti-B5-specific antibody responses were induced in mice after a single immunization. The antibody responses to all four antigens were significantly boosted after the second shot with all IgG titers >5 logs and highest being anti-A33 IgG. The high level of binding antibodies showed potent neutralizing capability against vaccinia virus. Specific IFN-γ responses were detected to all four antigens with the highest cellular response being that induced by the same antigen, A33. When evaluating the cross reactivity, equivalent or better serum IgG responses were seen in responses to corresponding monkeypox antigens A35, M1, A29 and B6, in comparison to vaccinia antigens. Apparently, the mRNA vaccine encoding four vaccinia antigens induced immunity not only to vaccinia virus but also to monkeypox, suggesting that the mRNA-ALAB may be a candidate for potential vaccine development against infection of monkeypox, smallpox and possibly other orthopoxviruses.
Two decades of molecular surveillance in Senegal reveal changes in known drug resistance mutations associated with historical drug use and seasonal malaria chemoprevention
Authors: Ndiaye Yaye Die , Wong Wesley , Thwing Julie , Schaffner Stephen S , Tine Abdoulaye , Diallo Mamadou Alpha , Deme Awa , Sy Mouhammad , Bei Amy K , Thiaw Alphonse B , Daniels Rachel , Ndiaye Tolla , Gaye Amy , Ndiaye Ibrahima Mbaye , Toure Mariama , Gadiaga Nogaye , Sene Aita , Sow Djiby , Garba Mamane N. , Yade Mamadou Samba , Dieye Baba , Diongue Khadim , Zoumarou Daba , Ndiaye Aliou , Gomis Jules , Fall Fatou Ba , Ndiop Medoune , Diallo Ibrahima , Sene Doudou , Macinnis Bronwyn , Seck Mame Cheikh , Ndiaye Mouhamadou , Badiane Aida S. , Hartl Daniel L. , Volkman Sarah K. , Wirth Dyann F. , Ndiaye Daouda
Published: April 2023

Drug resistance inPlasmodium falciparumis a major threat to malaria control efforts. We analyzed data from two decades (2000-2020) of continuous molecular surveillance ofP. falciparumparasite strains in Senegal to determine how historical changes in drug administration policy may have affected parasite evolution. We profiled several known drug resistance markers and their surrounding haplotypes using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole-genome sequence (WGS) based population genomics. We observed rapid changes in drug resistance markers associated with the withdrawal of chloroquine and introduction of sulfadoxine-pyrimethamine in 2003. We also observed a rapid increase inPfcrtK76T and decline inPfdhpsA437G starting in 2014, which we hypothesize may reflect changes in resistance or fitness caused by seasonal malaria chemoprevention (SMC). Parasite populations evolve rapidly in response to drug use, and SMC preventive efficacy should be closely monitored.
Boosting N-terminally anchored yeast surface display via structural insights intoS. cerevisiaePir proteins
Authors: Cezar Tea Martinić , Lozančić Mateja , Novačić Ana , Matičević Ana , Matijević Dominik , Vallee Beatrice , Mrša Vladimir , Teparić Renata , Žunar Bojan
Published: April 2023

Surface display co-opts yeast’s innate ability to embellish its cell wall with mannoproteins, thus converting the yeast’s outer surface into a growing and self-sustaining catalyst. However, the efficient toolbox for converting the enzyme of interest into its surface-displayed isoform is currently lacking, especially if the isoform needs to be anchored to the cell wall near the isoform’s N-terminus. Aiming to advance such N-terminally anchored surface display, we employedin silicoand machine-learning strategies to study the 3D structure, function, genomic organisation, and evolution of the Pir protein family, whose members evolved to covalently attach themselves near their N-terminus to the β-1,3-glucan of the cell wall. Through the newly-gained insights, we rationally engineered 14S. cerevisiaeHsp150 (Pir2)-based fusion proteins. We quantified their performance, uncovering guidelines for efficient yeast surface display while developing a construct that promoted a 2.5-fold more efficient display than the full-length Hsp150 and a Pir-tag, i.e., a peptide spanning only 4.5 kDa but promoting as efficient surface display as the full-length Hsp150. These constructs fortify the existing surface display toolbox, allowing for a prompt and routine refitting of any protein into its N-terminally anchored isoform.

Graphical abstract
The contested nature of third-sector organisations
Authors: Paterson Audrey , Jegers Marc , Lapsley Irvine
Published: April 2023

Purpose

The purpose of this paper is to reflect on the critical themes explored by the five papers in thisAccounting, Auditing & Accountability Journal (AAAJ)special issue and to offer a prospective analysis of issues for further research.

Design/methodology/approach

This reflective article provides a contextual outline of the challenges of managing and accounting for the third-sector during times of crisis.

Findings

Prior studies have covered aspects of trust, accountability and the use of accounting numbers for performance management in the third sector; however, little is known about how accounting numbers and disclosures can contribute to repairing donor trust and sensemaking following adverse events or how accounting numbers and disclosures can be used to navigate uncertainty. Drawing on accountability, trust and sensemaking literature, the papers in thisAAAJspecial issue contribute to closing this gap.

Research limitations/implications

Whilst the papers presented in thisAAAJspecial issue provide valuable insights into the challenges faced by third-sector organisations (TSOs) in times of crisis, several vital gaps that merit further investigations have been identified.

Originality/value

This paper andAAAJspecial issue provide a set of original empirical and theoretical contributions that can be used to advance further investigations into the complex issues faced by the third sector.
Patients experiences of therapeutic cannabis consumption in New Zealand
Authors: Hutton Fiona , Noller Geoff , McSherry Alice
Published: April 2023

Purpose

This study aims to explore people’s experiences of taking cannabis therapeutically and to gather some real-world evidence (RWE) about the products they were using, their efficacy and what kinds of positive or negative effect/s patients experienced. The focus of this discussion is the efficacy of cannabis for the participants in this study.

Design/methodology/approach

This was an exploratory study that used a mixed methods approach: a survey and semi-structured interviews. The data presented here focus on thematic analysis of five of the open-ended survey questions. Results from a purposive survey sample are also briefly reported. Interview data are not reported on here.

Findings

Across the sample (n = 213), 95.6% of participants reported that taking cannabis helped them with a number of conditions. The most common three themes across the thematic analysis were that cannabis helped with pain relief, sleep and anxiety. Negative effects, some of which related to having to source cannabis from the illicit market, were relatively minor and experienced by 28% (n = 58) of participants. An important finding was that 49% (n = 76) of those who said their use of prescribed medicines had decreased (n = 155), significantly decreased and in some cases stopped their use of prescribed medications.

Originality/value

This study reports on a sample of participants with clinically diagnosed conditions and adds to the RWE base about the efficacy of using cannabis for therapeutic purposes in the New Zealand context.
Standardised indicators for “resilient cities”: the folly of devising a technical solution to a political problem
Authors: Chmutina Ksenia , Lizarralde Gonzalo , von Meding Jason , Bosher Lee
Published: April 2023

Purpose

Driven by the New Urban Agenda and the Sustainable Development Goals, decision makers have been striving to reorientate policy debates towards the aspiration of achieving urban resilience and monitoring the effectiveness of adaptive measures through the implementation of standardised indicators. Consequently, there has been a rise of indicator systems measuring resilience. This paper aims to argue that the ambition of making cities resilient does not always make them less vulnerable, more habitable, equitable and just.

Design/methodology/approach

Using an inductive policy analysis of ISO standard 37123:2019 “Sustainable cities and communities — Indicators for resilient cities”, the authors examine the extent to which the root causes of risks are being addressed by the urban resilience agenda.

Findings

The authors show that the current standardisation of resilience fails to adequately address the political dimension of disaster risk reduction, reducing resilience to a management tool and missing the opportunity to address the socio-political sources of risks.

Originality/value

Such critical analysis of the Standard is important as it moves away from a hazard-centric approach and, instead, permits to shed light on the socio-political processes of risk creation and to adopt a more nuanced and sensitive understanding of urban characteristics and governance mechanisms.
Creative entrepreneurs and embeddedness in non-urban places: a resource exchange and network embeddedness logic
Authors: Leick Birgit , Gretzinger Susanne , Roddvik Irina Nikolskaja
Published: April 2023

Purpose

Drawing from resource-based theorising, the concept of network embeddedness and a process perspective on entrepreneurship, this paper establishes a conceptual framework to explain a multi-level and multi-locational network embeddedness of creative entrepreneurs in non-urban places. It challenges stylised facts about creative entrepreneurship as a predominantly urban phenomenon.

Design/methodology/approach

Based upon the conceptual framework for creative entrepreneurship in a non-urban place, an illustrative case study of small-scale creative-design entrepreneurs on the Lofoten Islands in Norway (2019) is utilised to discuss the framework.

Findings

The conceptual paper derives a fine-grained understanding about how creative entrepreneurship emerges and develops in non-urban places and contributes to a better understanding of how such places can nurture such entrepreneurship through multiple network embeddedness and resource-exchange configurations.

Research limitations/implications

The article will enable further empirical research that tests, validates and, if necessary, refines the framework established.

Practical implications

Creative entrepreneurs should use various resource-exchange combinations with diverse networks to become locally embedded in non-urban places. Public-policy managers need to be aware of this variety that may exist with the network embeddedness of such entrepreneurs to support them and develop the location through resource provisions.

Originality/value

The paper uses an original conceptual framework.
Why supply chain complexity prevails: mapping the complexity capability development process
Authors: Gerschberger Markus , Fawcet Stanley E. , Fawcett Amydee M. , Gerschberger Melanie
Published: April 2023

Purpose

Complexity has been called the 21st-century supply chain (SC) challenge. Most SC managers view it as a necessary evil, ever-present, costly and tough to manage, and few prioritize it. Still, anecdotes suggest some leverage it to drive operational excellence. This study aims to explore how they do it, delving into the development of a complexity management capability, under what circumstances it emerges and its effect on competitiveness.

Design/methodology/approach

To better understand why, and how, companies develop (or not) a distinctive SC complexity management capability, this study employed an inductive study of 10 leading European companies, each operating a complex SC.

Findings

Although SC complexity raises costs, increases disruptions and makes decision-making difficult, few companies have made complexity management a priority. Among those, most focus on reducing or absorbing complexity to improve operational excellence. A few invest to develop a distinctive SC complexity management capability. They manage complexity for market success. The interaction among competitive pressures, managerial attitudes and investments delineate a dynamic capability development process.

Research limitations/implications

Despite extensive research on complexity drivers, the tools used to manage SC complexity and the impact of SC complexity on performance, the interplay among factors that promote, or hinder, the development of an SC complexity capability continues to be poorly understood. By mapping the complexity capability development process, this study explicates a more nuanced approach to managing SC complexity that can yield a competitive edge.

Practical implications

SC complexity prevails because the dynamic, iterative complexity capability development process is overlooked. Managers can use the complexity capability roadmap to assess the cost/benefits of pursuing a distinctive complexity management capability more accurately.

Originality/value

This study demystifies the development of a complexity management capability, showing how some companies develop the capability to distinguish between value-added and value-dissipating complexity and thus become empowered to leverage SC complexity for competitive advantage.
TRIZ inventive principle in healthcare quality and innovation development
Authors: Tonjang Suebsakul , Thawesaengskulthai Natcha
Published: April 2023

Purpose

This research aimed to create inventive principles in managing quality and innovation systems that can be used as a guide for the development of effective innovation projects in hospitals.

Design/methodology/approach

Total quality and innovation management in healthcare (TQIM-H) framework and theory of inventive problem-solving (TRIZ) were integrated with results from in-depth interviews with 30 healthcare experts, resulting in TQIM-H inventive principle. The developed inventive principle was validated using 50 effective innovation projects from one of the largest healthcare conglomerates in Southeast Asia.

Findings

The TQIM-H inventive principle consisted of 7 dimensions and 72 procedures for creating innovation in hospitals under the medical quality framework. The principle effectively helps innovators develop innovative solutions that still strictly comply with medical guidelines.

Originality/value

Innovation is recognized as a critical factor that helps organizations adapt to global changes and increases the potential for competition, especially in hospitals. However, creating innovation in hospitals has a lower success rate than in other industries because, in general, ineffective innovation development strategies are used and the created innovation is not aligned with regulations and restrictions regarding healthcare quality in the healthcare system.
Those were the what? Contents of nostalgia, relative deprivation and radical right support
Authors: VERSTEEGEN PETER LUCA
Published: April 2023

Recent research suggests that emotions are a central motivation for radical right voting. One emotion that has gained particular interest is nostalgia: Radical right politicians use nostalgic rhetoric, and feeling nostalgic is associated with radical right support. However, while nostalgia is widely and frequently experienced, previous work differentiates personal contents of nostalgia (e.g., childhood) from group‐based contents (e.g., traditions) and suggests that only the latter is related to the radical right. But why does nostalgia, and specifically its group‐based content, matter? In the present paper, I argue that nostalgia evokes implicit comparisons between the past and the present. Using relative deprivation theory, I posit that group‐based nostalgia makes people subjectively evaluate society's present as worse than its past. In turn, this temporal group‐based relative deprivation is associated with attempts to restore the past through radical right voting. Personal nostalgia, instead, does not evoke equivalent experiences of personal relative deprivation and is, therefore, unrelated to radical right support. In preregistered analyses of representative panel data from the Netherlands, I show that group‐based nostalgia is more consistently related to radical right support than personal nostalgia. In subsequent exploratory analyses, I test the relative deprivation argument and find that group‐based relative deprivation does indeed mediate the relationship between group‐based nostalgia and radical right voting: People who long for the group‐based past are more likely to feel dissatisfied with the government and, in turn, consider voting for the radical right. In studying this mechanism, I connect recent work on emotional and relative deprivation explanations to radical right voting.
PSMA‐PET‐guided dose‐escalated volumetric arc therapy for newly diagnosed lymph node‐positive prostate cancer: 5 Year outcomes following the FROGG and EviQ node‐positive guidelines
Authors: Yap Shaun Zheng Liang , Armstrong Shreya , Aherne Noel , Shakespeare Thomas Philip
Published: April 2023

Introduction

The Royal Australian and New Zealand College of Radiologists (RANZCR) Faculty of Radiation Oncology Genitourinary Group (FROGG) guidelines and online EviQ protocols incorporate prostate‐specific membrane antigen (PSMA) positron emission tomography (PET)‐guided dose‐escalated intensity‐modulated radiation therapy (DE‐IMRT) for newly diagnosed lymph node (LN) positive prostate cancer. We evaluated late toxicity and efficacy outcomes following the FROGG and EviQ approach.

Methods

Patients with LN‐positive‐only metastases on PSMA‐PET imaging were offered curative therapy with 3 months neoadjuvant androgen deprivation therapy (ADT) followed by DE‐IMRT and 3 years adjuvant ADT. IMRT was delivered via volumetric arc therapy (VMAT). We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET‐positive LNs, and 60 Gy in 45 Fx to elective pelvic nodes, contoured using the PIVOTAL guidelines.

Results

Forty‐five patients were included. The median number of PET‐positive nodes boosted was 2 (range 1–6) and median boost volume 1.16 cc (range 0.15–4.14). Seventeen (38%) patients had PET‐positive nodes outside of PIVOTAL contouring guidelines. With 60 months median follow‐up, disease‐free, metastasis‐free, prostate cancer‐specific and overall survival were 88.1%, 95.3%, 100% and 91.5%. There were no in‐field nodal failures. Late grade 1, 2 and 3 gastrointestinal toxicities occurred in 4%, 2% and 0% of patients, and genitourinary toxicity in 18%, 18% and 4%. Lower limb grade 2 lymphoedema occurred in three patients (7%).

Conclusion

Outcomes following FROGG guidelines and EviQ are promising, with high long‐term disease control and low toxicity. Contouring guidelines require modification due to the high rate of PET‐positive nodes demonstrated beyond recommended coverage.
A second unveiling: Haplotig masking of the eastern oyster genome improves population‐level inference
Authors: Puritz Jonathan B. , Guo Ximing , Hare Matthew , He Yan , Hillier LaDeana W. , Jin Shubo , Liu Ming , Lotterhos Katie E. , Minx Pat , Modak Tejashree , Proestou Dina , Rice Edward S. , Tomlinson Chad , Warren Wesley C. , Witkop Erin , Zhao Honggang , Gomez‐Chiarri Marta
Published: April 2023

Genome assembly can be challenging for species that are characterized by high amounts of polymorphism, heterozygosity, and large effective population sizes. High levels of heterozygosity can result in genome mis‐assemblies and a larger than expected genome size due to the haplotig versions of a single locus being assembled as separate loci. Here, we describe the first chromosome‐level genome for the eastern oyster, Crassostrea virginica. Publicly released and annotated in 2017, the assembly has a scaffold N50 of 54 mb and is over 97.3% complete based on BUSCO analysis. The genome assembly for the eastern oyster is a critical resource for foundational research into molluscan adaptation to a changing environment and for selective breeding for the aquaculture industry. Subsequent resequencing data suggested the presence of haplotigs in the original assembly, and we developed a post hoc method to break up chimeric contigs and mask haplotigs in published heterozygous genomes and evaluated improvements to the accuracy of downstream analysis. Masking haplotigs had a large impact on SNP discovery and estimates of nucleotide diversity and had more subtle and nuanced effects on estimates of heterozygosity, population structure analysis, and outlier detection. We show that haplotig masking can be a powerful tool for improving genomic inference, and we present an open, reproducible resource for the masking of haplotigs in any published genome.
Epley maneuver for benign paroxysmal positional vertigo: Evidence synthesis for guidelines for reasonable and appropriate care in the emergency department
Authors: Khoujah Danya , Naples James G. , Oliveira J. e Silva Lucas , Edlow Jonathan A. , Gerberi Danielle J. , Carpenter Christopher R. , Bellolio Fernanda
Published: April 2023

Background

Canalith repositioning maneuvers (such as the Epley maneuver) are recommended by specialty guidelines for management of benign paroxysmal positional vertigo (BPPV) yet are frequently underutilized in the emergency department (ED).

Methods

We conducted a systematic review (SR) of SRs to summarize the evidence of Epley maneuver for the treatment of posterior canal (pc) BPPV in any setting. We included SRs of randomized controlled trials (RCTs) that compared Epley to control in adult patients with pc‐BPPV. Titles, abstracts, and full texts were screened in duplicate. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment was used to rate certainty of evidence. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported. Meta‐analysis of individual studies was conducted with random and fixed effects.

Results

From 2228 titles, seven SRs were selected for quality assessment. One review was of higher methodological quality, included only RCTs, and was the most current and comprehensive. Five of the 11 RCTs of the review, including 312 patients with pc‐BPPV diagnosed by Dix–Hallpike, were relevant to our question. Meta‐analysis of four RCTs (251 patients) showed the use of Epley (compared to control) was associated with higher complete resolution of vertigo at 1 week (OR 7.19, 95% CI 1.52–33.98, moderate certainty). Meta‐analysis of three RCTs (195 patients) showed the use of Epley was associated with higher conversion to negative Dix–Hallpike at 1 week (OR 6.67, 95% CI 1.52–33.98, moderate certainty). The number‐needed‐to‐treat was three. Meta‐analysis of the outcomes at 1 month, and when observational studies were included, showed similar results. No serious adverse effects were reported.

Conclusions

Symptoms of pc‐BPPV improve with the Epley maneuver. Emergency clinicians should become familiar with performing the Epley for BPPV. Further studies on ED implementation and clinician education of Epley are needed.
Gender diversity in urology scientific meetings: an analysis of the last nine years
Authors: Graham Vaite , Bray Gerard , Lyon Kate
Published: April 2023

Background

The importance of gender diversity is well recognized. Despite promising change in addressing gender disparity, there remains a significant gap in women's representation in urology. Worldwide, a lack of diversity has been observed at scientific meetings. This study analyses the trend in women's representation at the Urological Society of Australia and New Zealand Annual Scientific Meeting (USANZ ASM) over the last nine years.

Method

We retrospectively collected data from eight conference programs between 2014 and 2022, evaluating the trend in the proportion of women represented in various sections. A difference of proportions test was performed to determine whether a significant change was seen from year to year.

Results

A significant increase in women's representation was observed, the most significant increase was evident in the last three years, chairpersons increased from 5.9% to 44.1% (P = 0.003), international speakers from 11.7% to 39.1% (P ≤ 0.001), expert speakers from 19.1% to 42.0% (P = 0.002), and total speakers from 19.5% to 34.7% (P ≤ 0.001).

Conclusion

Our study shows that a significant increase in the representation of women at the USANZ ASM has been achieved over the last three years. Unfortunately, this increase in representation has not been mirrored in the number of women trainees and training applicants. Additionally, this increase in representation well exceeds the proportion of women who are USANZ members, and is unevenly distributed across topics. A positive change has been observed, the challenge remains in dealing with unconscious bias and balancing the fine line between inclusivity and tokenism.
Dual dialyzer hemodiafiltration: A new extracorporeal dialysis treatment modality for patients with end‐stage kidney disease
Authors: Glancey Gerald
Published: April 2023

Background

The introduction of high flux (HF) hemodialyzers and their application in single dialyzer hemodiafiltration (sdHDF) for patients on extracorporeal dialysis (ECD) therapy has improved the extraction of uremic toxins, including the low molecular weight protein (LMWP) beta 2 microglobulin (β2M, 11.6 kDa). Similar increases in the extraction of protein‐bound uremic toxins (PBUT) and larger LMWP (15‐50 kDa) remain elusive. High concomitant losses of albumin prohibit the use of medium cutoff (MCO) or protein‐losing hemodialyzers for sdHDF to increase the extraction of these molecules by convective transfer.

Methods

A new extracorporeal dialysis treatment modality, dual dialyzer hemodiafiltration (ddHDF), has been designed together with a mathematical model to compare its predicted performance to that of sdHDF in the extraction of solute. The extra process that distinguishes ddHDF from sdHDF is the secondary ultrafiltration and partial reinfusion of the effluent hemodiafiltrate from the primary hemodialyzer. This allows MCO and protein‐losing hemodialyzers to be used to increase the extraction of both LMWP and PBUT without excessive concomitant loss of albumin.

Results

Data from the mathematical model show that ddHDF could increase the extraction of smaller and larger LMWP by an extra 102% and 220%, respectively, compared to standard HF sdHDF, while restricting the loss of albumin to 0.83 g per hour of treatment. In using albumin as a recyclable carrier molecule for the extraction of PBUT from plasma ddHDF has the potential to increase PBUT reduction ratios (RR's) to 49% by convection alone. Even higher RR's are possible if the dialysate volume flow rate can be increased beyond 600 mL/min.

Conclusion

ddHDF provides an opportunity for a step change increase in the level of extraction of both larger LMWP and PBUT in patients with end‐stage kidney disease.
SARM1 promotes the neuroinflammation and demyelination through IGFBP2/NF‐κB pathway in experimental autoimmune encephalomyelitis mice
Authors: Zhang Jingjing , Jin Lingting , Hua Xin , Wang Mianxian , Wang Jiaojiao , Xu Xingxing , Liu Huitao , Qiu Haoyu , Sun Huankun , Dong Tianyingying , Yang Danlu , Zhang Xu , Wang Ying , Huang Zhihui
Published: April 2023

Aim

Multiple sclerosis (MS) is an autoimmune disease, and its typical characteristics are neuroinflammation and the demyelination of neurons in the central nervous system (CNS). Sterile alpha and TIR motif containing 1 (SARM1) is an essential factor mediating axonal degeneration and SARM1 deletion reduces the neuroinflammation in spinal cord injury. This study aimed to explore the roles of SARM1 and its underlying mechanisms in MS.

Methods

Experimental autoimmune encephalomyelitis (EAE, a model of MS) model was established. Immunostaining, western blot, electron microscope, and HE staining were used to examine the pathological manifestations such as inflammation, demyelination, and neuronal death in SARM1f/f EAE mice and SARM1Nestin‐CKO EAE mice. In addition, RNA‐seq, real‐time PCR and double‐immunostaining were used to examine the underlying mechanism of SARM1 in EAE mice.

Results

SARM1 was upregulated in neurons of the spinal cords of EAE mice. SARM1 knockout in CNS ameliorated EAE with less neuroinflammation, demyelination, and dead neurons. Mechanically, SARM1 knockout resulted in the reduction of insulin‐like growth factor (IGF)‐binding protein 2 (IGFBP2) in neurons of EAE mice, which might inhibit the neuroinflammation through inhibiting NF‐κB signaling. Finally, activation of NF‐κB partially aggravated the neuroinflammation and demyelination deficits of SARM1Nestin‐CKO EAE mice.

Conclusions

These results identified the unknown role of SARM1 in the promotion of neuroinflammation and demyelination and revealed a novel drug target pathway of SARM1/IGFBP2/NF‐κB for MS.
Notes on the female reproductive system of the red‐and‐black froghopper, Cercopis vulnerata Rossi, 1807 (Hemiptera: Cercopidae)‐light and electron microscopy studies
Authors: Özyurt Koçakoğlu Nurcan , Candan Selami , Arslan Hicret
Published: April 2023

The morphology of the female reproductive system in Cercopis vulnerata, an economically important species, was examined with light and scanning electron microscopy techniques. The female reproductive system of C. vulnerata has two ovaries, each containing 14 telotrophic meroistic ovarioles joined by two lateral oviducts that open in a common oviduct. In this type of ovarioles, the trophocytes within the germarium are transferred to the developing oocytes in the vitellarium via the nutritive cords. The oocytes in the vitellarium have three different development stages: previtello, vitello and choriogenesis. The ovarioles open in the lateral oviduct with a thin canal‐shaped pedicel. A pair of lateral oviducts opens distally into the common oviduct. The oviducts are surrounded by a monolayer cubical epithelium with deep folds toward the lumen and a thick muscle layer. A pair of spermatheca and a bursa copulatrix are seen near the common oviduct. Spermatheca has an elongated shape. The bursa copulatrix has an ovoid tube‐like structure. No work has been done on the female reproductive system of Cercopidae to date. This study was conducted to fill this gap and forms part of the female reproductive system morphology of this economically important insect.
Triptolide alleviates collagen‐induced arthritis in mice by modulating Treg/Th17 imbalance through the JAK/PTEN‐STAT3 pathway
Authors: Huang Yao , Ba Xin , Wang Hui , Shen Pan , Han Liang , Lin Weiji , Yan Jiahui , Chen Zhe , Tu Shenghao
Published: April 2023

Background

This study aimed to investigate the effects of triptolide (TP) on collagen‐induced arthritis (CIA) mice and the related mechanisms.

Methods

CIA mice were administered TP for 35 days. Mouse ankle joints and serum antibodies and cytokines were examined to assess the therapeutic effects of TP. The ratios of Treg, Th1 and Th17 cells were measured by flow cytometry and RT‐qPCR. Reverse docking was used to characterize the binding modes of TP against target proteins. The expression of the STAT3 pathway in CIA mice was evaluated by western blotting and immunofluorescence staining. Mouse spleen lymphocytes were extracted, and the expression of the STAT3 pathway after IL‐6 stimulation was analysed.

Results

TP could significantly alleviate joint swelling, reduce bone destruction and downregulate serum inflammation levels. TP improved the imbalance of Treg/Th17 cells in CIA mice. TP could form stable complexes with target proteins. TP significantly inhibited the activation of the JAK/PTEN‐STAT3 pathway in mice. Moreover, TP regulated the activation of the JAK1/2‐STAT3 signalling pathway in mouse spleen lymphocytes under inflammatory stimulation.

Conclusion

TP can inhibit inflammation and alleviate bone destruction in CIA mice. The underlying mechanism is related to the regulation of the imbalance of Treg/Th17 cells through the JAK/PTEN‐STAT3 pathway.
Factors associated with preemptive conservation under the U.S. Endangered Species Act
Authors: Treakle Tyler , Epanchin‐Niell Rebecca , Iacona Gwenllian D.
Published: April 2023

In recent decades, there has been an increasing emphasis on proactive efforts to conserve species being considered for listing under the U.S. Endangered Species Act (ESA) before they are listed (i.e., preemptive conservation). These efforts, which depend on voluntary actions by public and private land managers across the species’ range, aim to conserve species while avoiding regulatory costs associated with ESA listing. We collected data for a set of social, economic, environmental, and institutional factors that we hypothesized would influence voluntary decisions to promote or inhibit preemptive conservation of species under consideration for ESA listing. We used logistic regression to estimate the association of these factors with preemptive conservation outcomes based on data for a set of species that entered the ESA listing process and were either officially listed (n = 314) or preemptively conserved (n = 73) from 1996 to 2018. Factors significantly associated with precluded listing due to preemptive conservation included high baseline conservation status, low proportion of private land across the species’ range, small total range size, exposure to specific types of threats, and species’ range extending over several states. These results highlight strategies that can help improve conservation outcomes, such as allocating resources for imperiled species earlier in the listing process, addressing specific threats, and expanding incentives and coordination mechanisms for conservation on private lands.