bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the Spirit Move You? Environmental Spirituality
Authors: Booth Annie L.
Published: June 2023

This article looks at the idea of spirituality as it is discussed within ecophilosophical circles, particularly ecofeminism, bioregionalism, and deep ecology, as a means to improve human-nature interactions. The article also examines the use each ecophilosophy makes of a popular alternative to mainstream religion, that of Native American spiritualities, and problems inherent in adapting that alternative.
Community and Life-Chances: Risk Movements in the United States and Germany
Authors: Halfmann Jost
Published: June 2023

The connotations attached to the concept of ‘risk’ have changed over the last several decades. In particular, the image of risk, at least in the world's most economically advanced countries, has turned from predominantly positive to highly critical. A sociological look at this historic change reveals the emergence of a plurality of risk definitions that can be attributed to different risk cultures. We can distinguish risk cultures by their proximity to the dominant social practice of risk taking; namely risk cultures belong either to the centre or the periphery of society. Social movements that resist risky technologies are examples of a peripheral risk culture. Due to a certain concept of social community their perception of risk differs fundamentally from that of the centre. In addition, cultural variation across countries leads to different representations of risk-avoidance in social movements. This contribution illustrates these differences by comparing the American and German anti-nuclear movements.
Industrial Food for Thought: Timescapes of Risk1
Authors: Adam Barbara
Published: June 2023

This paper explores the temporal dimension of risks associated with the production, trade and consumption of food. The paper operates at many levels of substantive and theoretical analysis: it focuses on problems for understanding and action that arise from the invisibility of the hazards, explores the effects of those hazards on consumers and sets out the differences in risks that are faced by farmers, processors, traders and consumers. With its emphasis on that which tends to be disattended in conventional social science analysis – the temporal and the invisible – the paper has implications for social theory at the level of ontology and epistemology. It concludes with reflections on the role of social theory in such contemporary timescapes of risk.
Globalisation, Environmental Degradation and Ulrich Beck's Risk Society
Authors: Marshall Brent K.
Published: June 2023

This paper is organised in three interconnected parts. First, contemporary political economic approaches to understanding the structure of the global economic system are outlined and synthesised. Specifically, it is suggested that the current structural configuration of the globe is a transitional phase between the spatially-bounded configuration hypothesised by world-system theory and the configuration hypothesised by globalisation theorists. Second, the contemporary problem of environmental degradation is situated in a global structural context. Third, an outline and critique of Ulrich Beck's theory of the ‘Risk Society’ is presented to illustrate the increasing inadequacy of nation-state-centric theories in explaining the dynamic linkage between global capitalism and local environmental degradation.
Humans Valuing Nature: Synthesising Insights from Philosophy, Psychology and Economics
Authors: Lockwood Michael
Published: June 2023

A rational process for assessment of environmental policy options should be based on an appreciation of how humans value nature. Increased understanding of values will also contribute to the development of appropriate ways for us to relate to and manage natural areas. Over the past two decades, environmental philosophers have examined the notion that there is an intrinsic value in nature. Economists have attempted to define and measure the market and nonmarket economic values associated with decisions concerning natural areas. Psychologists have tried to assess the extent to which people believe in an intrinsic value in nature, and have also begun to work with economists to improve nonmarket valuation techniques. I briefly review the contributions made to our understanding of natural area value by environmental philosophy, psychology and economics, and develop a model that integrates insights from these disciplines. Components in the model include cognitions, held values, assigned values and various modes of value expression. I make recommendations for future validation, development and use of the model.
The Development of Environmental Thinking in Economics
Authors: Spash Clive L.
Published: June 2023

There has always been a sub-group of established economists trying to convey an environmental critique of the mainstream. This paper traces their thinking into the late 20th century via the development of associations and journals in the USA and Europe. There is clearly a divergence between the conformity to neo-classical economics favoured by resource and environmental economists and the acceptance of more radical critiques apparent in ecological economics. Thus, the progressive elements of ecological economics are increasingly incompatible with those practising neo-classical environmental economics who try to reduce all concepts to fit within the confines of their models. A group of people can be identified who teach that ecological economics is nothing more than a name for the link between mainstream economics and ecology. A new movement and paradigm are unnecessary for such ends. This viewpoint is argued to be inconsistent with the roots and ideas of the ecological economics movement. Ecological economics is seen here to be synthesising various types of economics (e.g., socialist, institutional, environmental) and moving back to explicit inclusion of ethical issues in the mode of classical political economy. This inevitably means rediscovering neglected past works and exploring new ways of thinking about socio-economics and the environment.
Nature is Already Sacred
Authors: Milton Kay
Published: June 2023

Environmentalists often argue that, in order to address fundamentally the harmful impact of their activities on the environment, western industrial societies need to change their attitude to nature. Specifically, they need to see nature as sacred, and to acknowledge that humanity is a part of nature rather than separate from it. In this paper, I seek to show that these two ideas are incompatible in the context of western culture. Drawing particularly on ideas expressed by western conservationists, I argue that nature is already seen as sacred, and that its sacredness depends on it being seen as separate from humanity, an idea which effectively contradicts the scientific knowledge on which many conservationists base their actions. Goodin's green theory of value is used as a source of ideas about why non-human nature is experienced as sacred, and can be extended to suggest that other values, such as ‘development’ and ‘progress’, are also seen as sacred.
Pragmatism, Adaptive Management, and Sustainability
Authors: Norton Bryan G.
Published: June 2023

The pragmatic conception of truth, anticipated by Henry David Thoreau and developed by C.S. Peirce and subsequent pragmatists, is proposed as a useful analogy for characterising ‘sustainability’. Peirce's definition of ‘truth’ provides an attractive approach to sustainability because (a) it re-focuses discussions of truth and objectivity from a search for ‘correspondence’ to an ‘external world’ (the ‘conform’ approach) to a more forward-looking (‘transform') approach; and (b) it emphasises the crucial role of an evolving, questioning community in the conduct of inquiry. Any successful definition of sustainability must share these characteristics with Peircean truth. While Peirce and John Dewey never reconciled their disagreements regarding the nature and task of ‘inquiry’, a pragmatist resolution of their differences is offered, arguing that we need both a logic of management sciences (logica utens) and a logic of pure science ( logica docens), which (perhaps among other differences) respond very differently to uncertainty. It is shown that adaptive management – an important approach to environmental management – can be understood as a first approximation of a logica utens for social learning in pursuit of solutions to environmental problems, and it is suggested that a pragmatist, transform approach to inquiry such as Dewey's may provide a way around the ‘fact-value’ gulf.
Modelling boredom in the EFL context: An investigation of the role of coping self-efficacy, mindfulness, and foreign language enjoyment
Authors: Fathi Jalil , Pawlak Mirosław , Kruk Mariusz , Naderi Milad
Published: June 2023

The aim of this study was to test a model of second language (L2) boredom based on coping self-efficacy (CSE), foreign language enjoyment (FLE), and mindfulness among English as a foreign language (EFL) learners. In so doing, 456 EFL learners from Iran took part in this study by completing an online survey which included scales tapping into the four latent constructs under investigation. Two-step structural equation modelling was utilized to analyse the data and examine the associations among the constructs. Results revealed that CSE and mindfulness positively affected FLE. Also, FLE was a direct negative predictor of L2 boredom. Concerning the mediation hypotheses, FLE was found to fully mediate the effect of mindfulness on boredom. However, FLE was a partial mediator between CSE and boredom. These findings provide a basis for important implications for L2 research and practice.
The hydrodynamic characteristics of autonomous underwater vehicles in rotating flow fields
Authors: Mitra A , Panda JP , Warrior HV
Published: June 2023

In this article, the hydrodynamic characteristics of Autonomous Underwater Vehicles (AUVs) are investigated and analyzed under the influence of rotating flow fields, which were generated in a recirculating water tank via a rotating propeller. Initially, experiments were carried out to measure flow field variables and quantities of Interest across the AUV in the presence of the rotating propeller while varying the rotational speed and the extent of rotational flow strength. The flow field across the AUV was measured using an Acoustic Doppler Velocimeter (ADV). These measured turbulent flow statistics were used to validate the Reynolds Stress Model (RSM) based numerical predictions in a commercial CFD solver. After preliminary validation of the turbulent flow statistics with the numerical predictions, a series of numerical simulations were performed to investigate the effect of the rotational flow field of the propeller on the drag, skin friction, and pressure coefficients of the AUV. The operating speed and location of the propeller were also varied to check their effects on the hydrodynamic performance of the AUV. The results provided in this article will be useful for the design optimization of AUVs cruising in shallow water where the flow is highly rotational because of wave-current interactions. Additionally, the results and analysis are relevant to study the design and operation of AUVs that have to operate in a group of unmanned underwater vehicles or near submarines and ships where the flow field is highly complex and such rotational effects are present.
A rare case of abnormal epithelial migration in the external auditory canal secondary to cotton bud abuse
Authors: Adhikari Tika Ram , Jamtsho Sonam
Published: June 2023

The outer third of external auditory canal is cartilaginous and contains pilosebaceous glands and hair follicles. The medial two third is bony, and the skin is devoid of these skin appendages and its secretions. It also has outward migratory property which makes the ear self-cleansing. Here we present an exceeding rare case of hair in the tympanic membrane causing distressing symptom of scratchy sensation, tinnitus, and otalgia. We hypothesize, it is the distortion of migratory pattern medially due to repeated otitis externa caused by abuse of cotton bud that led to presence of hair in the tympanic membrane.
Neurokinin receptor antagonists as potential non-hormonal treatments for vasomotor symptoms of menopause
Authors: Conklin Melissa , Santoro Nanette
Published: June 2023

Vasomotor symptoms of menopause (VMS), otherwise known as hot flashes, can significantly impact women’s quality of life. Up to 87% of women report hot flashes during or after their menopause transition, and can last for a median duration of 7.4 years. The current mainstay of treatment and the most effective treatment for VMS is hormone therapy with estrogen. However, hormone therapy is not without risk, and the discovery of an effective nonhormonal treatment option with neurokinin B receptor antagonists for VMS provides an encouraging and potentially practice-changing treatment option for all women. This review will discuss the pathophysiology and mechanism of action, as well as review the current compounds in development targeting the neurokinin receptors.
Transcriptomic analysis provides insight into the genetic regulation of shade avoidance in Aegilops tauschii
Authors: Xie Die , Hao Ming , Zhao Laibin , Chen Xue , Chen Xuejiao , Jiang Bo , Ning Shunzong , Yuan Zhongwei , Zhang Lianquan , Shu Kai , Zhang Yijing , Liu Dengcai , Wu Peipei
Published: June 2023

Background

Weeds are not only economically important but also fascinating models for studying the adaptation of species in human-mediated environments. Aegilops tauschii is the D-genome donor species of common wheat but is also a weed that influences wheat production. How shading stress caused by adjacent wheat plants affects Ae. tauschii growth is a fundamental scientific question but is also important in agriculture, such as for weed control and wheat breeding.

Result

The present study indicated that shade avoidance is a strategy of Ae. tauschii in response to shading stress. Ae. tauschii plants exhibited growth increases in specific organs, such as stem and leaf elongation, to avoid shading. However, these changes were accompanied by sacrificing the growth of other parts of the plants, such as a reduction in tiller number. The two reverse phenotype responses seem to be formed by systemically regulating the expression of different genes. Fifty-six genes involved in the regulation of cell division and cell expansion were found to be downregulated, and one key upstream negative regulator (RPK2) of cell division was upregulated under shading stress. On the other hand, the upregulated genes under shading stress were mainly enriched in protein serine/threonine kinase activity and carbon metabolism, which are associated with cell enlargement, signal transduction and energy supply. The transcription factor WRKY72 may be important in regulating genes in response to shading stress, which can be used as a prior candidate gene for further study on the genetic regulation of shade avoidance.

Conclusions

This study sheds new light on the gene expression changes and molecular processes involved in the response and avoidance of Ae. tauschii to shading stress, which may aid more effective development of shading stress avoidance or cultivars in wheat and other crops in the future.
Protocol for a prospective study evaluating circulating tumour cells status to predict radical prostatectomy treatment failure in localised prostate cancer patients (C-ProMeta-1)
Authors: Al-Hammouri Tarek , Almeida-Magana Ricardo , Lawrence Rachel , Duffy Tom , White Laura , Burke Edwina , Kudahetti Sakunthala , Collins Justin , Rajan Prabhakar , Berney Daniel , Gabe Rhian , Shaw Greg , Lu Yong-Jie
Published: June 2023

Background

Treatment decisions in prostate cancer (PCa) rely on disease stratification between localised and metastatic stages, but current imaging staging technologies are not sensitive to micro-metastatic disease. Circulating tumour cells (CTCs) status is a promising tool in this regard. The Parsortix® CTC isolation system employs an epitope-independent approach based on cell size and deformability to increase the capture rate of CTCs. Here, we present a protocol for prospective evaluation of this method to predict post radical prostatectomy (RP) PCa cancer recurrence.

Methods

We plan to recruit 294 patients diagnosed with unfavourable intermediate, to high and very high-risk localised PCa. Exclusion criteria include synchronous cancer diagnosis or prior PCa treatment, including hormone therapy. RP is performed according to the standard of care. Two blood samples (20 ml) are collected before and again 3-months after RP. The clinical team are blinded to CTC results and the laboratory researchers are blinded to clinical information. Treatment failure is defined as a PSA ≥ 0.2 mg/ml, start of salvage treatment or imaging-proven metastatic lesions. The CTC analysis entails enumeration and RNA analysis of gene expression in captured CTCs. The primary outcome is the accuracy of CTC status to predict post-RP treatment failure at 4.5 years. Observed sensitivity, positive and negative predictive values will be reported. Specificity will be presented over time.

Discussion

CTC status may reflect the true potential for PCa metastasis and may predict clinical outcomes better than the current PCa progression risk grading systems. Therefore establishing a robust biomarker for predicting treatment failure in localized high-risk PCa would significantly enhance guidance in treatment decision-making, optimizing cure rates while minimizing unnecessary harm from overtreatment.

Trial registration

ISRCTN17332543.
Impact of radiographic honeycombing on transplant free survival and efficacy of immunosuppression in fibrotic hypersensitivity pneumonitis
Authors: Adams Traci N. , Batra Kiran , Kypreos Margaret , Glazer Craig S.
Published: June 2023

Background

The distinction between hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF) was thought to be important due to the difference in mortality between the conditions as well as the response to treatment. However, recent work suggests that the clinical diagnosis may matter less than certain radiographic features, namely usual interstitial pneumonia (UIP) pattern. The purpose of this study is to evaluate whether radiographic honeycombing is more predictive of transplant-free survival (TFS) than other clinical, radiographic, or histologic findings that distinguish HP from IPF in the current guidelines and to evaluate the impact of radiographic honeycombing on the efficacy of immunosuppression in fibrotic HP.

Methods

We retrospectively identified IPF and fibrotic HP patients evaluated between 2003 and 2019. Univariable and multivariable logistic regression was performed for patients with fibrotic HP and IPF to evaluate TFS. To assess the impact of treatment with immunosuppression on TFS in fibrotic HP, a cox proportional hazard model adjusted for known predictors of survival in HP including age, gender, and baseline pulmonary function testing results was constructed, and p-interaction for the presence of honeycombing on high resolution computed tomography and use of immunosuppression was calculated.

Results

Our cohort included 178 with IPF and 198 with fibrotic HP. In a multivariable analysis, the presence of honeycombing had a greater impact on the TFS than the diagnosis of HP vs. IPF. Among the criteria used in the HP diagnostic guidelines, only typical HP scan impacted survival in a multivariable model, while identification of antigen and surgical lung biopsy findings had no impact on survival. We identified a trend toward worse survival on immunosuppression in those with HP with radiographic honeycombing.

Conclusion

Our data suggests that honeycombing and baseline pulmonary function testing have a greater impact on TFS than the clinical diagnosis of IPF vs. fibrotic HP and that radiographic honeycombing is a predictor of poor TFS in fibrotic HP. We suggest that invasive diagnostic testing including surgical lung biopsy may not be useful in predicting mortality in HP patients with honeycombing and may potentially increase risk of immunosuppression.
Developing the marine medicine syllabus for medical sciences students: a multiphase design study
Authors: Heydari Farshad , Nobakht Mohammad , Vahedian-Azimi Amir , Mirzamani Seyed Shahram , Moradian Seyed Tayeb , Ebadi Abbas , Morandini Morteza Kameli
Published: June 2023

Background

Marine medicine is one of the medical fields that deals with the health and safety of people related to the sea but the marine medicine syllabus for education to the students is not specified yet. The present study aimed to develop the marine medicine syllabus to medical sciences students education.

Methods

This study was conducted in three phases. First, a literature review was conducted to find the concepts and topics related to marine medicine. Second, a content analysis research method was conducted. Data collection was done first by using semi-structured interviews with the 12 experts in marine medicine. Sampling was purposeful and continued until data saturation was reached. The information obtained from the interviews was analyzed by conventional content analysis with Geranheim's method. The found topics in the literature review and content analysis of interviews were combined and formed the initial draft of the marine medicine syllabus, which was validated with the Delphi method in the third phase. The Delphi was conducted in two rounds and the panel consisted of 18 experts in the field of marine medicine. After the completion of each round, the items that had less than 80% consensus among the participants were removed and the remaining topics after round two formed the final syllabus of the marine medicine.

Results

The findings showed that the marine medicine syllabus should include an overview of marine medicine, health at sea, common physical diseases and injuries at sea, subsurface medicine and hyperbaric, safety action in marine incidents, medical care at sea, psychology at sea and medical examinations of people working at sea main topics and their sub topics.

Conclusions

Marine medicine is an extent and specialized medical field which has been neglected and it is necessary to teach this lesson to medical sciences students with the syllabus found in the present study.
Psychosocial assessment of adolescents and young adults in paediatric hospital settings: patient and staff perspectives on implementation of the e-HEEADSSS
Authors: Waller Daniel , Bailey Sophie , Zolfaghari Elham , Ho Jane , Feuerlicht Daniela , Ross Kirsty , Steinbeck Katharine
Published: June 2023

Background

The main causes of morbidity and mortality for adolescents and young adults are preventable and stem from psychosocial and behavioural concerns. Psychosocial assessments can help clinicians to identify and respond holistically to risks and strengths that may impact upon a young person’s physical and mental health. Despite broad support at a policy level, the implementation of routine psychosocial screening for young people remains varied in Australian health settings. The current study focused on the pilot implementation of a digital patient-completed psychosocial assessment (the e-HEEADSSS) at the Sydney Children’s Hospital Network. The aim of this research was to evaluate patient and staff barriers and facilitators to local implementation.

Methods

The research used a qualitative descriptive research design. Semi-structured interviews were conducted online with 8 young patients and 8 staff members who had completed or actioned an e-HEEADSSS assessment within the prior 5 weeks. Qualitative coding of interview transcripts was carried out in NVivo 12. The Consolidated Framework for Implementation Research guided the interview framework and qualitative analyses.

Results

Results demonstrated strong support for the e-HEEADSSS from patients and staff. Key reported facilitators included strong design and functionality, reduced time requirements, greater convenience, improved disclosure, adaptability across settings, greater perceived privacy, improved fidelity, and reduced stigma for young people. The key barriers were related to concerns over available resources, the sustainability and continuity of staff training, perceived availability of clinical pathways for follow-up and referrals, and risks related to off-site completions. Clinicians need to adequately explain the e-HEEADSSS assessment to patients, educate them about it, and make sure that they receive timely feedback on the results. Greater reassurance and education regarding the rigour of confidentiality and data handling procedures is required for patients and staff.

Conclusions

Our findings indicate that continued work is required to support the integration and sustainability of digital psychosocial assessments for young people at the Sydney Children’s Hospital Network. The e-HEEADSSS shows promise as an implementable intervention to achieve this goal. Further research is required to determine the scalability of this intervention across the broader health system.
Major depression disorder may causally associate with the increased atrial fibrillation risk: evidence from two-sample mendelian randomization analyses
Authors: Wang Lei , Ding Chunhua
Published: June 2023

Background

Observational studies have revealed a link between major depressive disorder (MDD) and a higher chance of developing atrial fibrillation (AF). It is still uncertain whether or not this correlation indicates a causal relationship. This research set out to evaluate the causal impact of MDD on AF.

Methods

To evaluate the causal relationship between MDD and AF, we employed a two-sample Mendelian randomization (MR) method. A new genome-wide association study (GWAS) with 500,199 participants was used to obtain an overview of the association of genetic variations with MDD. An additional GWAS incorporating 1,030,836 people provided data on the relationship between gene variants and AF. The inverse-variance weighted technique was utilized to assess the effect sizes. Sensitivity analysis included the use of other statistical approaches such as weighted median, Outlier, MR Pleiotropy Residual Sum, weighted mode, simple mode, and MR - Egger.

Results

By employing 47 single nucleotide polymorphisms (SNPs) as markers, MR analyses in random-effect inverse-variance weighted models found that genetically projected MDD was linked to an elevated incidence of AF (odds ratio [OR] = 1.098, 95% CI 1.000–1.206; P = 0.049). No gene pleiotropy was discovered as indicated by MR-Egger (intercept= -0.011, P = 0.169). Sensitivity analysis employing other MR techniques yielded reliable results.

Conclusion

This MR study established a causal relationship between genetically predicted MDD and an elevated risk of AF.
Reconsidering N component of cancer staging for T1-2N0-2M0 small-cell lung cancer: a retrospective study based on multicenter cohort
Authors: Wu Lei-Lei , Qiu Li-Hong , Chen Xiaolu , Yu Wan-Jun , Li Chong-Wu , Qian Jia-Yi , Liang Shen-Hua , Lin Peng , Long Hao , Zhang Lan-Jun , Li Zhi-Xin , Li Kun , Jiang Feng , Ma Guo-Wei , Xie Dong
Published: June 2023

Background

The current nodal (pN) classification still has limitations in stratifying the prognosis of small cell lung cancer (SCLC) patients with pathological classifications T1-2N0-2M0. Thus. This study aimed to develop and validate a modified nodal classification based on a multicenter cohort.

Materials and methods

We collected 1156 SCLC patients with pathological classifications T1-2N0-2M0 from the Surveillance, Epidemiology, and End Results database and a multicenter database in China. The X-tile software was conducted to determine the optimal cutoff points of the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). The Kaplan-Meier method, the Log-rank test, and the Cox regression method were used in this study. We classified patients into three pathological N modification categories, new pN#1 (pN0-#ELNs > 3), new pN#2 (pN0-#ELNs ≤ 3 or pN1-2-#LNR ≤ 0.14), and new pN#3 (N1-2-#LNR > 0.14). The Akaike information criterion (AIC), Bayesian Information Criterion, and Concordance index (C-index) were used to compare the prognostic, predictive ability between the current pN classification and the new pN component.

Results

The new pN classification had a satisfactory effect on survival curves (Log-rank P < 0.001). After adjusting for other confounders, the new pN classification could be an independent prognostic indicator. Besides, the new pN component had a much more accurate predictive ability in the prognostic assessment for SCLC patients of pathological classifications T1-2N0-2M0 compared with the current pN classification in the SEER database (AIC: 4705.544 vs. 4731.775; C-index: 0.654 vs. 0.617, P < 0.001). Those results were validated in the MCDB from China.

Conclusions

The multicenter cohort developed and validated a modified nodal classification for SCLC patients with pathological category T1-2N0-2M0 after surgery. Besides, we propose that an adequate lymph node dissection is essential; surgeons should perform and consider the situation of ELNs and LNR when they evaluate postoperative prognoses of SCLC patients.
Global, regional, and national burden of asthma and its attributable risk factors from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019
Authors: Wang Zhufeng , Li Yun , Gao Yi , Fu Yu , Lin Junfeng , Lei Xuedong , Zheng Jinping , Jiang Mei
Published: June 2023

Background

The burden of asthma in terms of premature death or reduced quality of life remains a huge issue. It is of great importance to evaluate asthma burden geographically and time trends from 1990 to 2019 and to assess the contributions of age, period, and cohort effects at global level.

Methods

Asthma prevalence, deaths, and disability adjusted life years (DALYs) as well as risk-attributable burden were collected from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 database and were compared by age and sex. The Smoothing Splines models were used to estimate the relationship between asthma DALYs and the sociodemographic index (SDI). The Age-Period-Cohort model was used to determine effects of ages, periods, and birth cohorts on disease rates.

Results

Between 1990 and 2019, the declines were 24.05% (95% uncertainty interval [UI] − 27.24 to − 20.82) in age-standardized asthma prevalence, 51.3% (− 59.08 to − 43.71) in mortality, and 42.55% (− 48.48 to − 36.61) in DALYs rate. However, the burden of asthma continued to rise, with an estimated 262.41 million prevalent cases globally (95% UI 224.05 to 309.45). Asthma caused greater DALYs in females than in males among people aged 20 years and older. The lowest age-standardized DALYs rate was observed at a SDI of approximately 0.70. The Longitudinal age curves showed an approximate W-shaped pattern for asthma prevalence and a likely J-shaped pattern for asthma mortality. The period effect on prevalence and mortality of asthma decreased from 1990 to 2019. Compared with the 1955–1959 birth cohort, the prevalence relative risk (RR) of asthma was highest in the 1905–1909 birth cohort, whereas the mortality RR continued to decline. At the global level, the percentages of high body-mass index, occupational asthmagens, and smoking contributing to DALYs due to asthma were 16.94%, 8.82%, and 9.87%, respectively.

Conclusions

Although the age-standardized rates of asthma burden declined in the past 30 years, the overall burden of asthma remains severe. High body mass index becomes the most important risk factor for DALYs due to asthma at the global level.
Nurse prescribing practices across the globe for medication-assisted treatment of the opioid use disorder (MOUD): a scoping review
Authors: Banka-Cullen Sonam Prakashini , Comiskey Catherine , Kelly Peter , Zeni Mary Beth , Gutierrez Ana , Menon Usha
Published: June 2023

Background

Despite the dramatic increase in opioid-related deaths in recent years, global access to treatment remains poor. A major barrier to people accessing Medication-assisted treatment of the opioid use disorder (MOUD) is the lack of providers who can prescribe and monitor MOUD. According to the World Drug Report, more young people are using drugs compared with previous generations and people in need of treatment cannot get it, women most of all. Nurse prescribers have the potential to enhance both access and treatment outcomes. Nurse prescribing practices do, however, vary greatly internationally. The aim of this scoping review is to explore nurse prescribing practices for MOUD globally with a view to informing equitable access and policies for people seeking MOUD.

Methods

This scoping review was informed by the preferred reporting items for systematic reviews and meta-analysis extension for scoping reviews (PRISMA-ScR). Electronic searches from 2010 to date were conducted on the following databases: PsycInfo, PubMed, Embase, and CINAHL. Only studies that met the eligibility criteria and described nurse prescribing policies and/or behaviours for MOUD were included.

Results

A total of 22 articles were included in the review which found several barriers and enablers to nurse prescribing of MOUD. Barriers included legislation constraints, lack of professional education and training and the presence of stigmatizing attitudes. Enablers included the presence of existing supportive services, prosocial messaging, and nurse prescriber autonomy.

Conclusion

The safety and efficacy of nurse prescribing of MOUD is well established, and its expansion can provide a range of advantages to people who are dependent on opiates. This includes increasing access to treatment. Nurse prescribing of MOUD can increase the numbers of people in treatment from ‘hard to reach’ cohorts such as rural settings, or those with less financial means. It holds significant potential to reduce a wide range of harms and costs associated with high-risk opiate use. To reduce drug-related death and the global burden of harm to individuals, families, and communities, there is an urgent need to address the two key priorities of nurse prescriber legislation and education. Both of which are possible given political and educational commitment.
Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury
Authors: Li Juanji , Xu Pengfei , Hong Ye , Xie Yi , Peng Mengna , Sun Rui , Guo Hongquan , Zhang Xiaohao , Zhu Wusheng , Wang Junjun , Liu Xinfeng
Published: June 2023

Background

Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play a major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis is a pro-inflammatory form of programmed cell death that has emerged as a new area of research in stroke. Nevertheless, the potential role of LCN2 in astrocyte pyroptosis remains unclear.

Methods

An ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in vivo. In this study, in vitro, oxygen–glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the LCN2 receptor) was inhibited by astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively. Histological and biochemical analyses were performed to assess astrocyte and neuron death. Additionally, the neurological deficits of mice were evaluated.

Results

LCN2 expression was significantly induced in astrocytes 24 h after stroke onset in the mouse MCAO model. Lcn2 knockout (Lcn2−/−) mice exhibited reduced infarct volume and improved neurological and cognitive functions after MCAO. LCN2 and its receptor 24p3R were colocalized in astrocytes. Mechanistically, suppression of 24p3R by AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation and the secretion of pro-inflammatory cytokines via LCN2, which was then reversed by Nig-induced NLRP3 inflammasome activation. Astrocyte pyroptosis was exacerbated in Lcn2−/− mice by intracerebroventricular administration of recombinant LCN2 (rLCN2), while this aggravation was restricted by blocking 24p3R or inhibiting NLRP3 inflammasome activation with MCC950.

Conclusion

LCN2/24p3R mediates astrocyte pyroptosis via NLRP3 inflammasome activation following cerebral ischemia/reperfusion injury.
Patients’ goals when initiating long-acting injectable buprenorphine treatment for opioid use disorder: findings from a longitudinal qualitative study
Authors: Neale Joanne , Parkin Stephen , Strang John
Published: June 2023

Background

Long-acting injectable buprenorphine (LAIB) is a new treatment for opioid use disorder that has been introduced against an international policy backdrop of recovery and person-centred care. This paper explores the goals that people want to achieve from LAIB to identify potential implications for policy and practice.

Methods

Data derive from longitudinal qualitative interviews conducted with 26 people (18 male; 8 female) initiating LAIB in England and Wales, UK (June 2021-March 2022). Participants were interviewed up to five times by telephone over six months (107 interviews in total). Transcribed interview data relating to each participant’s treatment goals were coded, summarised in Excel, and then analysed via a process of Iterative Categorization.

Results

Participants often articulated a desire to be abstinent without defining exactly what they meant by this. Most intended to reduce their dosage of LAIB but did not want to rush. Although participants seldom used the term ‘recovery’, almost all identified objectives consistent with current definitions of this concept. Participants articulated broadly consistent goals over time, although some extended the timeframes for achieving treatment-related goals at later interviews. At their last interview, most participants remained on LAIB, and there were reports that the medication was enabling positive outcomes. Despite this, participants were aware of the complex personal, service-level, and situational factors that hindered their treatment progress, understood the additional support they needed to achieve their goals, and voiced frustrations when services failed them.

Conclusions

There is a need for wider debate regarding the goals people initiating LAIB are seeking and the diverse range of positive treatment outcomes LAIB could potentially generate. Those providing LAIB should offer regular on-going contact and other forms of non-medical support so that patients have the best opportunity to succeed. Policies relating to recovery and person-centred care have previously been criticised for responsibilising patients and service users to take better care of themselves and to change their own lives. In contrast, our findings suggest that these policies may, in fact, be empowering people to expect a greater range of support as part of the package of care they receive from service providers.
The evolution of the mitochondrial disease diagnostic odyssey
Authors: Thompson John L. P. , Karaa Amel , Pham Hung , Yeske Philip , Krischer Jeffrey , Xiao Yi , Long Yuelin , Kramer Amanda , Dimmock David , Holbert Amy , Gorski Cliff , Engelstad Kristin M. , Buchsbaum Richard , Rosales Xiomara Q. , Hirano Michio
Published: June 2023

Background

Mitochondrial diseases often require multiple years and clinicians to diagnose. We lack knowledge of the stages of this diagnostic odyssey, and factors that affect it. Our goals are to report the results of the 2018 Odyssey2 (OD2) survey of patients with a medical diagnosis of mitochondrial disease; and to propose steps to reduce the odyssey going forward, and procedures to evaluate them.

Methods

Data are from the NIH-funded NAMDC-RDCRN-UMDF OD2 survey (N = 215). The main outcomes are Time from symptom Onset to mitochondrial disease Diagnosis (TOD) and Number of Doctors Seen during this diagnostic process (NDOCS).

Results

Expert recoding increased analyzable responses by 34% for final mitochondrial diagnosis and 39% for prior non-mitochondrial diagnosis. Only one of 122 patients who initially saw a primary care physician (PCP) received a mitochondrial diagnosis, compared to 26 of 86 (30%) who initially saw a specialist (p < 0.001). Mean TOD overall was 9.9 ± 13.0 years, and mean NDOCS 6.7 ± 5.2. Mitochondrial diagnosis brings extensive benefits through treatment changes and increased membership in and support of advocacy groups.

Conclusions

Because TOD is long and NDOCS high, there is great potential for shortening the mitochondrial odyssey. Although prompt patient contact with primary mitochondrial disease specialists, or early implementation of appropriate tests, may shorten the diagnostic odyssey, specific proposals for improvement require testing and confirmation with adequately complete, unbiased data across all its stages, and appropriate methods. Electronic Health Record (EHRs) may help by accessing diagnostic codes early, but their reliability and diagnostic utility have not been established for this group of diseases.
Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS): new cases, systematic literature review, and associations with CSF1R-ALSP
Authors: Dulski Jarosław , Souza Josiane , Santos Mara Lúcia , Wszolek Zbigniew K.
Published: June 2023

CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS). The former is increasingly recognized, and disease-modifying therapy was introduced; however, literature is scarce on the latter. This review analyzes BANDDOS and discusses similarities and differences with CSF1R-ALSP.

We systematically retrieved and analyzed the clinical, genetic, radiological, and pathological data on the previously reported and our cases with BANDDOS. We identified 19 patients with BANDDOS (literature search according to the PRISMA 2020 guidelines: n = 16, our material: n = 3). We found 11 CSF1R mutations, including splicing (n = 3), missense (n = 3), nonsense (n = 2), and intronic (n = 2) variants and one inframe deletion. All mutations disrupted the tyrosine kinase domain or resulted in nonsense-mediated mRNA decay. The material is heterogenous, and the presented information refers to the number of patients with sufficient data on specific symptoms, results, or performed procedures. The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1). Dysmorphic features were present in 7/17 cases. Neurological symptoms included speech disturbances (n = 13/15), cognitive decline (n = 12/14), spasticity/rigidity (n = 12/15), hyperactive tendon reflex (n = 11/14), pathological reflexes (n = 8/11), seizures (n = 9/16), dysphagia (n = 9/12), developmental delay (n = 7/14), infantile hypotonia (n = 3/11), and optic nerve atrophy (n = 2/7). Skeletal deformities were observed in 13/17 cases and fell within the dysosteosclerosis – Pyle disease spectrum. Brain abnormalities included white matter changes (n = 19/19), calcifications (n = 15/18), agenesis of corpus callosum (n = 12/16), ventriculomegaly (n = 13/19), Dandy-Walker complex (n = 7/19), and cortical abnormalities (n = 4/10). Three patients died in infancy, two in childhood, and one case at unspecified age. A single brain autopsy evidenced multiple brain anomalies, absence of corpus callosum, absence of microglia, severe white matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications.

In conclusion, BANDDOS presents in the perinatal period or infancy and has a devastating course with congenital brain abnormalities, developmental delay, neurological deficits, osteopetrosis, and dysmorphic features. There is a significant overlap in the clinical, radiological, and neuropathological aspects between BANDDOS and CSF1R-ALSP. As both disorders are on the same continuum, there is a window of opportunity to apply available therapy in CSF1R-ALSP to BANDDOS.
“Because it is a rare disease…it needs to be brought to attention that there are things out of the norm”: a qualitative study of patient and physician experiences of Wilson disease diagnosis and management in the US
Authors: Bailey Karen M , Sahota Navdeep , To Uyen , Hedera Peter
Published: June 2023

Background

Wilson disease (WD) is a genetic disorder of copper metabolism that leads to copper accumulation in various organs, primarily the liver and brain, resulting in heterogenous hepatic, neurologic, and psychiatric symptoms. Diagnosis can occur at any age, requiring lifelong treatment, which can involve liver transplantation. This qualitative study aims to understand the wider patient and physician experience of the diagnosis and management of WD in the US.

Methods

Primary data were collected from 1:1 semi structured interviews with US-based patients and physicians and thematically analyzed with NVivo.

Results

Twelve WD patients and 7 specialist WD physicians (hepatologists and neurologists) were interviewed. Analysis of the interviews revealed 18 themes, which were organized into 5 overarching categories: (1) Diagnosis journey, (2) Multidisciplinary approach, (3) Medication, (4) The role of insurance, and (5) Education, awareness, and support. Patients who presented with psychiatric or neurological symptoms reported longer diagnostic journeys (range 1 to 16 years) than those presenting with hepatic symptoms or through genetic screening (range 2 weeks to 3 years). All were also affected by geographical proximity to WD specialists and access to comprehensive insurance. Exploratory testing was often burdensome for patients, but receipt of a definitive diagnosis led to relief for some. Physicians emphasized the importance of multidisciplinary teams beyond hepatology, neurology, and psychiatry and recommended a combination of chelation, zinc, and a low-copper diet; however, only half the patients in this sample were on a chelator, and some struggled to access prescription zinc due to insurance issues. Caregivers often advocated for and supported adolescents with their medication and dietary regimen. Patients and physicians recommended more education and awareness for the healthcare community.

Conclusions

WD requires the coordination of care and medication among several specialists due to its complex nature, but many patients do not have access to multiple specialties due to geographical or insurance barriers. Because some patients cannot be treated in Centers of Excellence, easy access to reliable and up-to-date information is important to empower physicians, patients, and their caregivers in managing the condition, along with general community outreach programs.
CATI: an efficient gene integration method for rodent and primate embryos by MMEJ suppression
Authors: Chen Hongyu , Liu Xingchen , Li Lanxin , Tan Qingtong , Li Shiyan , Li Li , Li Chunyang , Fu Jiqiang , Lu Yong , Wang Yan , Sun Yidi , Luo Zhen-Ge , Lu Zongyang , Sun Qiang , Liu Zhen
Published: June 2023

The efficiency of homology-directed repair (HDR) plays a crucial role in the development of animal models and gene therapy. We demonstrate that microhomology-mediated end-joining (MMEJ) constitutes a substantial proportion of DNA repair during CRISPR-mediated gene editing. Using CasRx to downregulate a key MMEJ factor, Polymerase Q (Polq), we improve the targeted integration efficiency of linearized DNA fragments and single-strand oligonucleotides (ssODN) in mouse embryos and offspring. CasRX-assisted targeted integration (CATI) also leads to substantial improvements in HDR efficiency during the CRISPR/Cas9 editing of monkey embryos. We present a promising tool for generating monkey models and developing gene therapies for clinical trials.