bluuebunny/crossref_metadata_2025 huggingface dataset:
Do global innovation networks influence the status of global value chains? Based on a patent cooperation network perspective
Authors: Xu Shenyi , Lian Ganghui , Song Miaoyuan , Xu Aiting
Published: July 2024

Under the impact of economic globalization, the internationalization of production and trade has given rise to global value chains (GVCs) and global innovation networks (GINs); however, few studies have explored the link between these two networks. This paper constructs a global innovation cooperation network based on patent cooperation data and then analyzes the impact of different network characteristics on improving global value chain status. Empirical research shows that the characteristics of GINs significantly affect GVC status; the higher the eigenvector centrality and network connectivity, the higher the country’s GVC status. Moreover, a higher degree of constraint is associated with a lower GVC status for the country concerned. The heterogeneity analysis further reveals apparent differences in the impact of GINs on different countries, manifesting as a catalytic effect in developed countries and as a disincentive in emerging economies; the effect is less apparent in developing countries. This paper provides theoretical support for the development of technological innovation activities and provides a reference for government departments to formulate policies on cross-border technological innovation cooperation.
Fragmented property rights and their risks on foreclosed housing: a qualitative comparative analysis based on judicial auctions in China
Authors: Qian Xingyu
Published: July 2024

During China’s transition towards land and housing marketization in the 1980s to 1990s, a series of legal and policy arrangements led to the separation of land ownership from land-use rights, followed by the separation of housing ownership from land-use rights. This has institutionally fragmented the housing property rights, allowing properties to be financialized as collaterals. Consequently, the fragmentation of housing property rights inflicts substantial risks on judicial auctions of foreclosed housing. As China’s real estate sector is grappling with a mounting debt crisis, it becomes imperative to enhance the efficiency of judicial auctions to address bank debts and stabilize the housing financial system. By employing the cs-QCA method with a dataset comprising 136 cases of foreclosed properties, this study reveals the critical role of various configurations of property-rights risks in determining the outcome of judicial auctions. Additionally, it identifies the importance of credible commitments offered by the courts in mitigating property-rights risks. The research expects to provide practical and theoretical insights for China’s courts and financial institutions to manage foreclosed properties effectively.
Co-designing inclusive excellence in higher education: Students’ and teachers’ perspectives on the ideal online learning environment using the I-TPACK model
Authors: Saenen Liesbet , Hermans Katrien , Do Nascimento Rocha Maristela , Struyven Katrien , Emmers Elke
Published: July 2024

Online education remains challenging for many institutions of higher education (HE). COVID-19 lockdowns have demonstrated inequalities, underlining the need for more study on its effects on access and engagement. The recent I-TPACK model enables teachers to utilize technological resources to meet diverse learning needs, improve accessibility, and create engaging learning experiences for all students. Online inclusive learning environments (LEs) necessitate a comprehensive understanding of teacher and student needs and perspectives within HE, a level of education that is currently understudied. Moreover, in inclusive and online education, their voices are underrepresented in research and policy discussions, despite their importance. This study aims to investigate how teachers and students in HE articulate their preferred inclusive online LE and therefore adopted a qualitative research approach including homogeneous focus groups, directed by the I-TPACK model. Results present students’ and teachers’ key elements and conditions of an inclusive online LE. However, there is little preparation and common language on how to implement them. Online LEs’ inclusion potential is still underappreciated. This research provides policy suggestions closely aligned with practical application and highlights the necessity of venturing beyond the comfort zone exploring inclusive online practices, as presented by the I-TPACK model.
Elementary Predicates and Related Categories
Authors: Franco Ludovico
Published: July 2024

This book offers a fresh perspective on how natural languages encode grammatical relations, by delving into the interplay between oblique cases, adpositions, serial verbs, and applicatives. This book reveals, through a series of case studies, the pervasive role of the 'inclusion' relator across diverse linguistic contexts. Departing from traditional views that obliques lack interpretive content, this work presents a unified conceptual framework of relations in grammar. Drawing on minimalist principles, the book posits a preeminence of the lexicon in syntactic projection, shedding light on the underlying ontology of language. By exploring cross-categorial variation and syncretism, it outlines an inventory of primitives shaping morpho-syntactic derivations.
Exploring the Sociopragmatics of Online Humor
Authors: Tsakona Villy
Published: July 2024

This monograph explores the diverse sociopragmatic functions and meanings of humorous discourse in various online contexts affecting its use. To this end, an analytical model is proposed which takes into consideration the aspects of context which are relevant to the production and reception of humor, and hence to its sociopragmatic analysis. The model is employed for addressing research questions such as the following: Why may an utterance/text be intended and perceived as humorous by some speakers and fail for others? How and why may speakers attempt to regulate language use through humor? Why and how may the same humorous utterance/text engender diverse and contradictory interpretations? How do speakers create social groups and project social identities through humor? How could the sociopragmatic analysis of humor form the basis for teaching about humor within a critical literacy framework?
Effect of dielectric material on the uniformity of nanosecond pulsed dielectric barrier discharge
Authors: ZHOU 周 Wenhao 文昊 , ZHANG 张 Dongxuan 东璇 , DUAN 段 Xiaohui 晓慧 , ZHU 祝 Xi 曦 , LIU 刘 Feng 峰 , FANG 方 Zhi 志
Published: July 2024

Dielectric barrier discharge (DBD) is considered as a promising technique to produce large volume uniform plasma at atmospheric pressure, and the dielectric barrier layer between the electrodes plays a key role in the DBD processes and enhancing discharge uniformity. In this work, the uniformity and discharge characteristics of the nanosecond (ns) pulsed DBD with dielectric barrier layers made of alumina, quartz glass, polycarbonate (PC), and polypropylene (PP) are investigated via discharge image observation, voltage-current waveform measurement and optical emission spectral diagnosis. Through analyzing discharge image by gray value standard deviation method, the discharge uniformity is quantitatively calculated. The effects of the space electric field intensity, the electron density (N
e), and the space reactive species on the uniformity are studied with quantifying the gap voltage U
g and the discharge current I
g, analyzing the recorded optical emission spectra, and simulating the temporal distribution of N
e with a one-dimensional fluid model. It is found that as the relative permittivity of the dielectric materials increases, the space electric field intensity is enhanced, which results in a higher N
e and electron temperature (T
e). Therefore, an appropriate value of space electric field intensity can promote electron avalanches, resulting in uniform and stable plasma by the merging of electron avalanches. However, an excessive value of space electric field intensity leads to the aggregation of space charges and the distortion of the space electric field, which reduce the discharge uniformity. The surface roughness and the surface charge decay are measured to explain the influences of the surface properties and the second electron emission on the discharge uniformity. The results in this work give a comprehensive understanding of the effect of the dielectric materials on the DBD uniformity, and contribute to the selection of dielectric materials for DBD reactor and the realization of atmospheric pressure uniform, stable, and reactive plasma sources.
Memories of Spain in Sylvia Townsend Warner and John Cowper Powys
Authors: Connor John T
Published: July 2024

This chapter pairs Sylvia Townsend Warner and John Cowper Powys as mid-century Left historical novelists, neither of whom quite neatly inhabited the national-popular form of the genre: Powys as a former communist fellow-traveller turned anarchist, and Warner as a ‘Third Period’ recruit to the Party whose primary allegiance was to the cause of peasant struggle and revolution in the countryside. Both writers were passionate about the Civil War in Spain, however, and it was to raise awareness and funds for the Republican side that in 1937 they briefly shared a Communist Party stage. The chapter records the impress of Spain on their major fictions of the 1940s. It reads Powys’ dark-age romance Porius (1951) as a sophisticated reckoning with the ethics of historical agency anchored in the failure of the anarchist social experiment in Catalonia, and Warner’s The Corner That Held Them (1948) as a fable of feudalism.
Parables of Survival
Authors: Connor John T
Published: July 2024

This epilogue traces a line of descent from the mid-century to the far side of postmodernism and our own contemporary moment. It begins with Raymond Williams in the 1980s urging writers and critics to break from the ‘long and bitter impasse of a once liberating modernism’. Williams’ target was the modernism of the cultural Cold War, its academic, New Left, and mass-cultural inscriptions, and the postmodernism he saw as its heir. In their place, he looked to install a countercanon of mid-century texts, including a communist historical novel by the Welsh writer Gwyn Thomas. This chapter assesses the influence of Thomas’s All Things Betray Thee (1949) on Williams’ own historical novel trilogy, People of the Black Mountains (1989–90). It argues that Williams took from his mid-century writers a conception of politics that now resonates with contemporary attempts to revitalize activist theory and revive the historical novel as a social movement genre.
Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON): a multicentre, open-label, blinded-outcome, randomised controlled trial
Authors: Bogaerts Jonathan M K , Gussekloo Jacobijn , de Jong-Schmit Bianca E M , Le Cessie Saskia , Mooijaart Simon P , van der Mast Roos C , Achterberg Wilco P , Poortvliet Rosalinde K E
Published: July 2024

Background

Based on observational studies and randomised controlled trials (RCTs), the benefit–harm balance of antihypertensive treatment in older adults with dementia is unclear.

Objective

To assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia.

Design

Open-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365.

Subjects

Dutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492).

Measurements

Co-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks.

Results

From 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6–89.5] years; 79.5% female; median SBP 134 [IQR 123–146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI –2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference − 2.5 [95% CI –6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98–2.79]). All 32-week outcomes favoured usual care.

Conclusion

Halfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit–harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia.
The use of natural language processing for the identification of ageing syndromes including sarcopenia, frailty and falls in electronic healthcare records: a systematic review
Authors: Osman Mo , Cooper Rachel , Sayer Avan A , Witham Miles D
Published: July 2024

Background

Recording and coding of ageing syndromes in hospital records is known to be suboptimal. Natural Language Processing algorithms may be useful to identify diagnoses in electronic healthcare records to improve the recording and coding of these ageing syndromes, but the feasibility and diagnostic accuracy of such algorithms are unclear.

Methods

We conducted a systematic review according to a predefined protocol and in line with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Searches were run from the inception of each database to the end of September 2023 in PubMed, Medline, Embase, CINAHL, ACM digital library, IEEE Xplore and Scopus. Eligible studies were identified via independent review of search results by two coauthors and data extracted from each study to identify the computational method, source of text, testing strategy and performance metrics. Data were synthesised narratively by ageing syndrome and computational method in line with the Studies Without Meta-analysis guidelines.

Results

From 1030 titles screened, 22 studies were eligible for inclusion. One study focussed on identifying sarcopenia, one frailty, twelve falls, five delirium, five dementia and four incontinence. Sensitivity (57.1%–100%) of algorithms compared with a reference standard was reported in 20 studies, and specificity (84.0%–100%) was reported in only 12 studies. Study design quality was variable with results relevant to diagnostic accuracy not always reported, and few studies undertaking external validation of algorithms.

Conclusions

Current evidence suggests that Natural Language Processing algorithms can identify ageing syndromes in electronic health records. However, algorithms require testing in rigorously designed diagnostic accuracy studies with appropriate metrics reported.
Relationships of Office, Ambulatory, and Self-measured Blood Pressure With Cardiac, Renal, and Atherosclerotic Biomarkers
Authors: Narita Keisuke , Hoshide Satoshi , Kario Kazuomi
Published: July 2024

BACKGROUND

Previous studies with several limitations have comparatively analyzed the relationship between ambulatory blood pressure (BP) and self-measured BP and biomarkers of organ damage. This study extends this line of research by examining the relationship between ambulatory and self-measured BP and cardiac, renal, and atherosclerotic biomarkers in outpatients at cardiovascular risk.

METHODS

In 1,440 practice outpatients who underwent office, ambulatory, and self-measured BP monitoring, we assessed the relationships of each BP with organ damage biomarkers including b-type natriuretic peptide (BNP), echocardiographic left ventricular mass index (LVMI), urine albumin-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV).

RESULTS

In the comparison of correlation, self-measured systolic BP (SBP) was more strongly correlated to log-transformed (Ln) BNP (n = 1,435; r = 0.123 vs. r = −0.093, P < 0.001), LVMI (n = 1,278; r = 0.223 vs. r = 0.094, P < 0.001), Ln-UACR (n = 1,435; r = 0.244 vs. r = 0.154, P = 0.010), and baPWV (n = 1,360; r = 0.327 vs. r = 0.115, P < 0.001) than daytime ambulatory SBP. In the linear regression models including office, ambulatory, and self-measured SBP, only self-measured SBP was significantly related to Ln-BNP (P = 0.016) and LVMI (P < 0.001). In the logistic regression models for the top quartile of LVMI, adding self-measured SBP improved the model predictability (P = 0.027), but adding daytime ambulatory SBP did not. However, adding daytime ambulatory SBP improved the model predictability in the logistic model for the top quartile of baPWV including office and self-measured SBP (P = 0.030).

CONCLUSIONS

Our study findings suggested that self-measured BP was associated with cardiac biomarkers independent of ambulatory BP.
Stereospecific reduction of 2′S-configured strigolactones by cowpea OPR3 enzymes
Authors: Suzawa Shota , Yamauchi Misa , Homma Masato , Yamauchi Yasuo , Mizutani Masaharu , Wakabayashi Takatoshi , Sugimoto Yukihiro
Published: July 2024

Strigolactones (SLs), plant-derived apocarotenoids, serve dual roles as phytohormones and rhizosphere signaling molecules. While exogenous administration of SLs to plants aids in studying their functions, the metabolic destiny of these administered SLs remains poorly elucidated. Our previous research demonstrated that among synthetic SL GR24 stereoisomers administered to cowpea (Vigna unguiculata), 2′-epi-GR24 undergoes selective reduction at the C-3′,4′ double bond in its D-ring. In this investigation, we isolated proteins from cowpea roots based on SL reducing activity and identified 12-oxophytodienoate reductase 3 homologs (VuOPR3s) as contributors to this reduction. Enzymatic assays conducted with recombinant proteins revealed that VuOPR3s exhibited a preference for reducing activity toward 2′S-configured SLs, including 2′-epi-GR24. This specificity for 2′S-configured SLs was congruent with that observed for orobanchol produced by cowpea and its stereoisomers. These findings suggest that exogenously administered SLs undergo enzymatic stereoselective reduction, underscoring the importance of considering stereospecificity when interpreting data obtained from SL usage.
LarvaTagger: manual and automatic tagging of Drosophila larval behaviour
Authors: Laurent François , Blanc Alexandre , May Lilly , Gándara Lautaro , Cocanougher Benjamin T , Jones Benjamin M W , Hague Peter , Barré Chloé , Vestergaard Christian L , Crocker Justin , Zlatic Marta , Jovanic Tihana , Masson Jean-Baptiste
Published: July 2024

Motivation

As more behavioural assays are carried out in large-scale experiments on Drosophila larvae, the definitions of the archetypal actions of a larva are regularly refined. In addition, video recording and tracking technologies constantly evolve. Consequently, automatic tagging tools for Drosophila larval behaviour must be retrained to learn new representations from new data. However, existing tools cannot transfer knowledge from large amounts of previously accumulated data. We introduce LarvaTagger, a piece of software that combines a pre-trained deep neural network, providing a continuous latent representation of larva actions for stereotypical behaviour identification, with a graphical user interface to manually tag the behaviour and train new automatic taggers with the updated ground truth.

Results

We reproduced results from an automatic tagger with high accuracy, and we demonstrated that pre-training on large databases accelerates the training of a new tagger, achieving similar prediction accuracy using less data.

Availability and implementation

All the code is free and open source. Docker images are also available. See gitlab.pasteur.fr/nyx/LarvaTagger.jl.
Semiparametric efficiency gains from parametric restrictions on propensity scores
Authors: Kono Haruki
Published: July 2024

We explore how much knowing a parametric restriction on propensity scores improves semiparametric efficiency bounds in the potential outcome framework. For stratified propensity scores, considered as a parametric model, we derive explicit formulas for the efficiency gain from knowing how the covariate space is split. Based on these, we find that the efficiency gain decreases as the partition of the stratification becomes finer. For general parametric models, where it is hard to obtain explicit representations of efficiency bounds, we propose a novel framework that enables us to see whether knowing a parametric model is valuable in terms of efficiency even when it is high dimensional. In addition to the intuitive fact that knowing the parametric model does not help much if it is sufficiently flexible, we discover that the efficiency gain can be nearly zero even though the parametric assumption significantly restricts the space of possible propensity scores.
Racially Determined Case Characteristics: Exploring Disparities in the Use of Sentencing Factors in England and Wales
Authors: Guilfoyle Eoin , Pina-Sánchez Jose
Published: July 2024

There is little understanding of how documented ethnic disparities in sentencing outcomes in England and Wales come to be and, consequently, how to address them. We argue that disparities in sentence outcomes could stem from how cases are constructed. We hypothesize that case characteristics determined through a high degree of judicial discretion and an assessment of the offender have a high risk of being racially determined, and therefore, operate as precursors of ethnic disparities in sentencing. We test this using Crown Court Sentencing Survey and Court Proceedings data. We identify three sentencing factors (remorse, good character and ability to rehabilitate) clearly favouring White offenders. We contextualize their operation and argue that all three should be classified as racially determined and sources of ethnic disparity. We conclude by setting out targeted policy solutions.
Unpaid Care Work Time and Women’s Employment Status: Evidence from India
Authors: Tripathi Saumya , Zhai Fuhua , Azhar Sameena
Published: July 2024

Using the first Indian 2019 Time Use Survey, we investigate the association between women’s time spent on unpaid care work (UCW) and their employment status and whether this association differs by socio-demographic characteristics such as age, marital status, education level and household size, controlling for religion, social group status, household monthly expenditure and geographical location (e.g. rural versus urban settings). Using multinomial logistic regression, an inverse association was found between women’s UCW and their employment status. An hour increase in women’s time spent on UCW decreased their odds of employment, self-employment or pursuing higher education by 38 per cent, 27 per cent and 34 per cent, respectively. According to a decomposition analysis, almost 80 per cent of the odds ratios for employment status were due to increased time spent on UCW rather than the influence of socio-demographic characteristics. Findings underscore the need for integrating care provisions into the broader social and economic agenda for the country.
A patient’s experience of progressive hemifacial atrophy
Authors: Larney Conor , Watson Rosemarie , Murray Dylan , Irvine Alan D
Published: July 2024

Progressive hemifacial atrophy is a rare idiopathic disorder that can have a significant impact on quality of life. In this article, a patient describes his experience of the condition.
Empathy incites a stable prosocial decision bias
Authors: Saulin Anne , Ma Yina , Hein Grit
Published: July 2024

Empathy toward suffering individuals serves as potent driver for prosocial behavior. However, it remains unclear whether prosociality induced by empathy for another person’s pain persists once that person’s suffering diminishes. To test this, participants underwent functional magnetic resonance imaging while performing a binary social decision task that involved allocation of points to themselves and another person. In block one, participants completed the task after witnessing frequent painful stimulation of the other person, and in block two, after observing low frequency of painful stimulation. Drift-diffusion modeling revealed an increased initial bias toward making prosocial decisions in the first block compared with baseline that persisted in the second block. These results were replicated in an independent behavioral study. An additional control study showed that this effect may be specific to empathy as stability was not evident when prosocial decisions were driven by a social norm such as reciprocity. Increased neural activation in dorsomedial prefrontal cortex was linked to empathic concern after witnessing frequent pain and to a general prosocial decision bias after witnessing rare pain. Altogether, our findings show that empathy for pain elicits a stable inclination toward making prosocial decisions even as their suffering diminishes.
Vertebral fractures in patients with CKD and the general population: a call for diagnosis and action
Authors: Gifre Laia , Massó Elisabet , Fusaro Maria , Haarhaus Mathias , Ureña Pablo , Cozzolino Mario , Mazzaferro Sandro , Calabia Jordi , Peris Pilar , Bover Jordi
Published: July 2024

Vertebral fractures (VFs) are the most common osteoporotic fractures in the general population, and they have been associated with high mortality, decreased quality of life, and high risk of subsequent fractures, especially when recent, multiple, or severe. Currently, VF diagnosis and classification determine fracture risk and the most appropriate anti-osteoporotic treatment. However, VFs are clearly underdiagnosed, especially in patients with chronic kidney disease (CKD), and CKD-associated osteoporosis has been disregarded until recently. VFs are associated with higher morbidity and mortality, and their prevalence and incidence differ depending on the grade of renal dysfunction (CKD G1–G5) and/or the type of renal replacement therapy (dialysis or transplantation). In addition to classical risk factors [such as higher age, female sex, reduced bone mineral density, diabetes and steroid use], various other factors have been associated with an increased risk of VFs in CKD, including CKD grade, haemodialysis vintage, time since renal transplantation, low or high intact parathyroid hormone and phosphate levels, and/or vitamin D and K1 deficiencies. Importantly, several clinical societies have recently modified their algorithms according to the fracture risk classification (including the presence of VFs) and determined the most appropriate anti-osteoporotic treatment for the general population. However, there are no specific guidelines addressing this topic in patients with CKD despite an important paradigm shift regarding the prognostic value of bone mineral density in 2017 after the publication of the CKD-Mineral and Bone Disorder Kidney Disease: Improving Global Outcomes guidelines. A proactive attitude towards diagnosis, treatment, and research is proposed to avoid therapeutic nihilism.
Risk factors for major bleeding in patients with atrial fibrillation and CKD G3–G5D on oral anticoagulants
Authors: Welander Frida , Renlund Henrik , Själander Anders
Published: July 2024

Background

Patients with chronic kidney disease (CKD) and atrial fibrillation (AF) on oral anticoagulants (OACs) are at high risk of bleeding. Determinants of major bleeding risk in OAC users with AF and CKD are not well established and available bleeding score systems do not perform well in CKD. This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3–5D.

Methods

We conducted a Swedish register-based cohort study including patients with AF and CKD G3–5D on warfarin or direct OACs (DOACs) between 2009 and 2018. Data were collected from high-quality registers including the Swedish Renal Registry and Auricula, a register for AF and OACs. Risk factors for major bleeding were investigated with Cox regression analysis.

Results

Of 2453 included patients, 59% were on warfarin (time in therapeutic range 67%) and 41% on DOACs. Major bleeding rates were 8.9/100 patient-years. Factors associated with increased bleeding risk were glomerular filtration rate category, G5/5D versus G3 {hazard ratio [HR] 1.92 [95% confidence interval (CI) 1.43–2.56]}, previous gastrointestinal bleeding [HR 1.77 (95% CI 1.39–2.25)], previous other bleeding [HR 1.33 (95% CI 1.09–1.62)], congestive heart failure [HR 1.36 (95% CI 1.11–1.68)], male sex [HR 1.28 (95% CI 1.03–1.60)] and vascular disease [HR 1.35 (95% CI 1.01–1.79)].

Conclusion

Patients with AF and G3–5D on OACs are at a high risk of bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding. The present study also shows an association between OAC-associated bleeding and male sex, congestive heart failure and vascular disease. Knowledge about determinants of bleeding in advanced CKD is essential when deciding on when to anticoagulate or not.
Integrating multiple kidney function markers to predict all-cause and cardiovascular disease mortality: prospective analysis of 366 758 UK Biobank participants
Authors: Fujii Ryosuke , Melotti Roberto , Köttgen Anna , Teumer Alexander , Giardiello Daniele , Pattaro Cristian
Published: July 2024

Background

Reduced kidney function is a risk factor of cardiovascular and all-cause mortality. This association was demonstrated for several kidney function markers, but it is unclear whether integrating multiple measured markers may improve mortality risk prediction.

Methods

We conducted an exploratory factor analysis (EFA) of serum creatinine– and cystatin C–based estimated glomerular filtration rate [eGFRcre and eGFRcys; derived by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) equations], blood urea nitrogen (BUN), uric acid and serum albumin among 366 758 participants in the UK Biobank without a history of kidney failure. Fitting Cox proportional hazards models, we compared the ability of the identified latent factors to predict overall mortality and mortality by cardiovascular disease (CVD), also considering CVD-specific causes like coronary heart disease (CHD) and cerebrovascular disease.

Results

During 12.5 years of follow-up, 26 327 participants died from any cause, 5376 died from CVD, 2908 died from CHD and 1116 died from cerebrovascular disease. We identified two latent factors, EFA1 and EFA2, both representing kidney function variations. When using the CKD-EPI equation, EFA1 performed like eGFRcys, with EFA1 showing slightly larger hazard ratios for overall and CVD-related mortality. At 10 years of follow-up, EFA1 and eGFRcys showed moderate discrimination performance for CVD-related mortality, outperforming all other kidney indices. eGFRcre was the least predictive marker across all outcomes. When using the EKFC equation, eGFRcys performed better than EFA1 while all other results remaining similar.

Conclusions

While EFA is an attractive approach to capture the complex effects of kidney function, eGFRcys remains the most practical and effective measurement for all-cause and CVD mortality risk prediction.
Hypoaldosteronism due to a novel SEC61A1 variant successfully treated with fludrocortisone
Authors: Karpman Diana , Lindström Martin L , Möller Mattias , Ivarsson Sofie , Kristoffersson Ann-Charlotte , Bekassy Zivile , Fogo Agnes B , Elfving Maria
Published: July 2024

Background

Genetic variants in SEC61A1 are associated with autosomal dominant tubulointerstitial kidney disease. SEC61A1 is a translocon in the endoplasmic reticulum membrane and variants affect biosynthesis of renin and uromodulin.

Methods

A patient is described that presented at 1 year of age with failure-to-thrive, kidney failure (glomerular filtration rate, GFR, 18 ml/min/1.73m2), hyperkalemia and acidosis. Genetic evaluation was performed by whole genome sequencing.

Results

The patient has a novel de novo heterozygous SEC61A1 variant, Phe458Val. Plasma renin was low or normal, aldosterone was low or undetectable and uromodulin was low. Kidney biopsy at 2 years exhibited subtle changes suggestive of tubular dysgenesis without tubulocystic or glomerulocystic lesions and with renin staining of the juxtaglomerular cells. The patient experienced extreme fatigue due to severe hypotension attributed to hypoaldosteronism and at 8 years of age fludrocortisone treatment was initiated with marked improvement in her well-being. Blood pressure and potassium normalized. Biopsy at 9 years showed extensive glomerulosclerosis and mild tubulointerstitial fibrosis, as well as tubular mitochondrial abnormalities, without specific diagnostic changes. Her GFR improved to 54 ml/min/1.73m2.

Conclusions

As the renin-angiotensin system promotes aldosterone release, and the patient had repeatedly undetectable aldosterone levels, the SEC61A1 variant presumably contributed to severe hypotension. Treatment with a mineralocorticoid had a beneficial effect and corrected the electrolyte and acid-base disorder. We suggest that the increased blood pressure hemodynamically improved the patient's kidney function.
Advances in nucleic acid-targeted therapies for cardiovascular disease prevention
Authors: Makhmudova Umidakhon , Steinhagen-Thiessen Elisabeth , Volpe Massimo , Landmesser Ulf
Published: July 2024

Nucleic acid-based therapies are being rapidly developed for prevention and management of cardiovascular diseases (CVD). Remarkable advancements have been achieved in the delivery, safety, and effectiveness of these therapeutics in the past decade. These therapies can also modulate therapeutic targets that cannot be sufficiently addressed using traditional drugs or antibodies. Among the nucleic acid-targeted therapeutics under development for CVD prevention are RNA-targeted approaches, including antisense oligonucleotides (ASO), small interfering RNAs (siRNA), and novel genome editing techniques.

Genetic studies have identified potential therapeutic targets that are suggested to play a causative role in development and progression of CVD. RNA- and DNA-targeted therapeutics can be particularly well delivered to the liver, where atherogenic lipoproteins and angiotensinogen (AGT) are produced. Current targets in lipid metabolism include proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein A (ApoA), apolipoprotein C3 (ApoC3), angiopoietin-like 3 (ANGPTL3). Several large-scale clinical development programs for nucleic acid-targeted therapies in cardiovascular prevention are under way, which may also be attractive from a therapy adherence point of view, given the long action of these therapeutics. In addition to genome editing, the concept of gene transfer is presently under assessment in preclinical and clinical investigations as a potential approach for addressing low-density lipoprotein receptor deficiency. Furthermore, ongoing research is exploring the use of RNA-targeted therapies to treat arterial hypertension by reducing hepatic angiotensinogen (AGT) production.

This review summarizes the rapid translation of siRNA and ASO therapeutics as well as gene editing into clinical studies to treat dyslipidemia and arterial hypertension for CVD prevention. It also outlines potential innovative therapeutic options that are likely relevant to the future of cardiovascular medicine.
ImmRNA: a database of RNAs associated with tumor immunity
Authors: Shen Fangfang , Li Zelian , Wu Pengfei , Wang Jinpeng
Published: July 2024

The relationship between different ribonucleic acids (RNAs) and tumor immunity has been widely investigated. However, a systematic description of tumor immune-related RNAs in different tumors is still lacking. We collected the relationship of tumor immune-related RNAs from the published literature and presented them in a user-friendly interface, “ImmRNA” (http://www.immrna.cn/), to provide a resource to study immune-RNA-cancer regulatory relations. The ImmRNA contains 49 996 curated entries. Each entry includes gene symbols, gene types, target genes, downstream effects, functions, immune cells, and other information. By rearranging and reanalyzing the data, our dataset contains the following key points: (i) providing the links between RNAs and the immune in cancers, (ii) displaying the downstream effects and functions of RNAs, (iii) listing immune cells and immune pathways related to RNA function, (iv) showing the relationship between RNAs and prognostic outcomes, and (v) exhibiting the experimental methods described in the article. ImmRNA provides a valuable resource for understanding the functions of tumor immune-related RNAs.

Database URL:  http://www.immrna.cn/
Influence of examiner calibration on clinical and MRI diagnosis of temporomandibular joint disc displacement: a systematic review and meta-analysis
Authors: Maracci Lucas Machado , Savegnago Gleica Dal Ongaro , Antoniazzi Raquel Pippi , Marquezan Mariana , Silva Tatiana Bernardon , Liedke Gabriela Salatino
Published: July 2024

Objectives

This study aimed to verify the accuracy of clinical protocols for the diagnosis of disc displacement (DD) compared with MRI, considering examiners’ calibration.

Methods

PubMed, Cochrane (Central), Scopus, Web of Science, LILACS, Embase, Science Direct, Google Scholar, and DANS EASY Archive databases were searched. Two reviewers independently screened and selected the studies. A meta-analysis was conducted using the R Statistical software. Results are shown using sensitivity and specificity, and 95% confidence intervals.

Results

Of the 20 studies included in the systematic review, only three were classified as low risk of bias. Seventeen studies were included in the meta-analysis. Compared to MRI, clinical protocols showed overall sensitivity and specificity of 0.75 (0.63-0.83) and 0.73 (0.59-0.84) for DD diagnosis, respectively. For DD with reduction, sensitivity was 0.64 (0.48-0.77) and specificity was 0.72 (0.48-0.87). For DD without reduction, sensitivity was 0.58 (0.39-0.74) and specificity 0.93 (0.83-0.97). Only 8 studies reported examiner calibration when performing clinical and/or MRI evaluation; nevertheless, calibration showed a tendency to improve the diagnosis of DD.

Conclusion

The sensitivity and specificity of clinical protocols in the diagnosis of DD are slightly below the recommended values, as well as the studies lack calibration of clinical and MRI examiners. Examiner calibration seems to improve the diagnosis of DD.
Reoperative extended arch repair for acute type A aortic dissection after previous cardiac surgery: insights from a relatively young redo series
Authors: Zhang Yixiao , Wang Yulin , Liu Fangyu , Chen Qiyi , Shao Kejie , Lai Hao , Wang Chunsheng , Ji Qiang
Published: July 2024

OBJECTIVES

To evaluate the impact of previous cardiac surgery (PCS) on clinical outcomes after reoperative extended arch repair for acute type A aortic dissection.

METHODS

This study included 37 acute type A aortic dissection patients with PCS (PCS group) and 992 without PCS (no-PCS group). Propensity score-matching yielded a subgroup of 36 pairs (1:1). In-hospital outcomes and mid-term survival were compared between the 2 groups.

RESULTS

The PCS group was older (56.7 ± 14.2 vs 52.2 ± 12.6 years, P = 0.036) and underwent a longer cardiopulmonary bypass (median, 212 vs 183 min, P < 0.001) compared with the no-PCS group. Operative death occurred in 88 (8.6%) patients, exhibiting no significant difference between groups (13.5% vs 8.4%, P = 0.237). Major postoperative morbidity was observed in 431 (41.9%) patients, also showing no difference between groups (45.9% vs 41.7%, P = 0.615). Moreover, the multivariable logistic regression analysis revealed that PCS was not significantly associated with operative mortality (adjusted odds ratio 2.58, 95% confidence interval 0.91–7.29, P = 0.075) or major morbidity (adjusted odds ratio 1.92, 95% confidence interval 0.88–4.18, P = 0.101). The 3-year cumulative survival rates were 71.1% for the PCS group and 83.9% for the no-PCS group (log-rank P = 0.071). Additionally, Cox regression indicated that PCS was not significantly associated with midterm mortality (adjusted hazard ratio 1.40, 95% confidence interval 0.44–4.41, P = 0.566). After matching, no significant differences were found between groups in terms of operative mortality (P > 0.999), major morbidity (P > 0.999) and midterm survival (P = 0.564).

CONCLUSIONS

No significant differences were found between acute type A aortic dissection patients with PCS and those without PCS regarding in-hospital outcomes and midterm survival after extended arch repair.
Predicting fragility fractures based on frailty and bone mineral density among rural community-dwelling older adults
Authors: Lee Jeongmin , Kim Jinyoung , Jeong Chaiho , Ha Jeonghoon , Lim Yejee , Baek Ki-Hyun
Published: July 2024

Objective

We aim to investigate the association between bone mineral density (BMD) measurement and fragility fractures and assess the predictive value of combining BMD measurement and frailty for fracture risk assessment.

Methods

This retrospective cohort study analyzed data from 5126 rural Koreans in the Chungju Metabolic Disease Cohort study. Frailty was defined using Fried's frailty phenotype. Fractures were assessed via structured medical interviews. Adjusted odds ratios (ORs) were calculated considering age, sex, body mass index, behavior, BMD, handgrip strength, medications, and comorbidities.

Results

The study cohort consisted of 5126 participants comprising 1955 (38.1%) males and 3171 (61.9%) females. Osteoporosis significantly increased the fracture risk across all types, except vertebral fracture, with adjusted OR (95% CI) of 1.89 (1.23-3.47) for any fracture, 2.05 (1.37-2.98) for hip fracture, 2.18 (1.06-4.50) for other fracture, and 1.71 (1.03-3.63) for major osteoporotic fracture (MOF). Frail individuals exhibited significantly increased risk for any fracture (OR 2.12; 95% CI, 1.21-3.71), vertebral fracture (2.48; 1.84-3.61), hip fracture (2.52; 1.09-3.21), other fracture (2.82; 1.19-8.53), and MOF (1.87; 1.01-3.47). The combination of frailty and BMD further increased the risks, with frail individuals demonstrating elevated ORs across BMD categories. In subgroup analyses, men showed a significant association between frailty with osteoporosis in hip fracture and MOF. Frail women with osteoporosis exhibited the highest risks for all fractures, particularly vertebral (OR 5.12; 95% CI, 2.07-9.68) and MOF (OR 5.19; 95% CI, 2.07-6.61). Age-specific analysis revealed that individuals aged 70 and older exhibited markedly higher fracture risks compared with those under 70. The combination of frailty and low BMD further elevated the fracture risk. Frailty was applied with BMD and demonstrated superior risk prediction for MOF compared with that with either score alone (area under the curve 0.825; P = .000).

Conclusions

Combining frailty with BMD provides a more accurate fracture risk assessment for individuals over 50 years.
Longer school schedules, childcare and the quality of mothers’ employment
Authors: Berthelon Matias , Kruger Diana , Lauer Catalina , Tiberti Luca , Zamora Carlos
Published: July 2024

Better employment quality can improve personal well-being, social cohesion, and inclusive growth and development. Yet good quality jobs – associated with greater well-being – are less accessible to women than men. While it is understood that policies balancing family and work lead to greater female labour participation, this paper investigates whether one such policy – increased childcare – improves the quality of jobs where mothers are employed. The context we analyse is a nationwide school reform in Chile that extended school schedules for primary school-aged children, providing childcare services. We combine administrative data of the phase-in of the policy with panel data of individual mothers’ employment outcomes and socio-economic characteristics. We estimate a fixed-effects model that controls for mothers’ unobserved heterogeneity and identifies the effect of the policy from plausibly exogenous temporal and spatial variations in access to schools with long schedules and exogenous exposure to the policy. We find a positive effect of childcare on several measures of employment quality and gender gaps within the couple. Our evidence suggests that the mechanism driving the impact is the implicit subsidy to the cost of childcare, affecting the opportunity cost of mothers’ time. In addition, we find heterogeneous results by mothers’ education level. Access to childcare through longer primary school schedules can increase household welfare and can play a role in reducing income and gender inequalities.
Extracellular Vesicle MicroRNAs as Predictive Biomarkers in Postoperative Delirium After Spine Surgery: Preliminary Study
Authors: Cho Young-Eun , Kim Jeongmin , Vorn Rany , Cho Hyeonmi , Baek Wonhee , Park Hyunki , Yun Sijung , Kim Hyung-Suk , Cashion Ann K , Gill Jessica , Koo Bon-Nyeo , Lee Hyangkyu
Published: July 2024

Postoperative delirium (POD) can cause poor patient outcomes in older adults who undergo surgery. In this study, we tested plasma extracellular vesicle (EV) miRNAs obtained before the delirium event to find predictive POD biomarkers after spine surgery. We recruited patients who are more than 70 years old and have undergone spine surgery. Finally, POD patients (n = 31) were included, with no-POD patients matched in age, sex, medical history, and type of surgery (n = 31). Peripheral blood was collected from patients in the operating room after the operation was completed. EVs were isolated from plasma, and the 798 miRNA expression level from EVs was measured using a NanoString platform. Sixty-two patients were included in the study; all were Korean, 67.7% were females, and the median age was 75 years. Preoperative medical history was not statistically different between no-POD and POD patients except for hypertension and the American Society of Anesthesiologists physical status. From the miRNA profiling, we identified 142 significantly differentially expressed miRNAs in POD patients compared with no-POD patients, which are associated with psychological/neurological disorders. The top 10 differentially expressed miRNAs including miR-548ar-5p and miR-627-5p were all upregulated in POD patients and the results were validated using qRT-PCR from the independent sets of samples (n = 96). We demonstrated the potential of plasma EV-miRNAs as predictive biomarkers to identify the risk group of POD after spine surgery. It also provides opportunities for future studies investigating the role of EV-miRNAs in delirium pathology.