bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-thermal atmospheric-pressure positive pulsating corona discharge in degradation of textile dye Reactive Blue 19 enhanced by Bi2O3 catalyst
Authors: PETROVIĆ Milica , RADIVOJEVIĆ Dragan , RANČEV Saša , VELINOV Nena , KOSTIĆ Miloš , BOJIĆ Danijela , BOJIĆ Aleksandar
Published: November 2023

In this work, monoclinic Bi2O3 was applied for the first time, to the best of our knowledge, as a catalyst in the process of dye degradation by a non-thermal atmospheric-pressure positive pulsating corona discharge. The research focused on the interaction of the plasma-generated species and the catalyst, as well as the role of the catalyst in the degradation process. Plasma decomposition of the anthraquinone reactive dye Reactive Blue 19 (RB 19) was performed in a self-made reactor system. Bi2O3 was prepared by electrodeposition followed by thermal treatment, and characterized by x-ray diffraction, scanning electron microscopy and energy-dispersive x-ray techniques. It was observed that the catalyst promoted decomposition of plasma-generated H2O2 into •OH radicals, the principal dye-degrading reagent, which further attacked the dye molecules. The catalyst improved the decolorization rate by 2.5 times, the energy yield by 93.4% and total organic carbon removal by 7.1%. Excitation of the catalyst mostly occurred through strikes by plasma-generated reactive ions and radical species from the air, accelerated by the electric field, as well as by fast electrons with an energy of up to 15 eV generated by the streamers reaching the liquid surface. These strikes transferred the energy to the catalyst and created the electrons and holes, which further reacted with H2O2 and water, producing •OH radicals. This was indentified as the primary role of the catalyst in this process. Decolorization reactions followed pseudo first-order kinetics. Production of H2O2 and the dye degradation rate increased with increase in the input voltage. The optimal catalyst dose was 500 mg∙dm−3. The decolorization rate was a little lower in river water compared with that in deionized water due to the side reactions of •OH radicals with organic matter and inorganic ions dissolved in the river water.
Gyro-Landau-fluid simulations of impurity effects on ion temperature gradient driven turbulence transport
Authors: LIU 刘 Yifei 逸飞 , LI 李 Jiquan 继全
Published: November 2023

The effects of impurities on ion temperature gradient (ITG) driven turbulence transport in tokamak core plasmas are investigated numerically via global simulations of microturbulence with carbon impurities and adiabatic electrons. The simulations use an extended fluid code (ExFC) based on a four-field gyro-Landau-fluid (GLF) model. The multispecies form of the normalized GLF equations is presented, which guarantees the self-consistent evolution of both bulk ions and impurities. With parametric profiles of the cyclone base case, well-benchmarked ExFC is employed to perform simulations focusing on different impurity density profiles. For a fixed temperature profile, it is found that the turbulent heat diffusivity of bulk ions in a quasi-steady state is usually lower than that without impurities, which is contrary to the linear and quasi-linear predictions. The evolutions of the temperature gradient and heat diffusivity exhibit a fast relaxation process, indicating that the destabilization of the outwardly peaked impurity profile is a transient state response. Furthermore, the impurity effects from different profiles can obviously influence the nonlinear critical temperature gradient, which is likely to be dominated by linear effects. These results suggest that the improvement in plasma confinement could be attributed to the impurities, most likely through adjusting both heat diffusivity and the critical temperature gradient.
Spatiotemporal variability in population demography and morphology of the habitat-forming macroalga Saccorhiza polyschides in the Western English Channel
Authors: Salland Nora , Wilding Catherine , Jensen Antony , Smale Dan A
Published: November 2023

Background and Aims

Large brown macroalgae serve as foundation organisms along temperate and polar coastlines, providing a range of ecosystem services. Saccorhiza polyschides is a warm-temperate kelp-like species found in the northeast Atlantic, which is suggested to have proliferated in recent decades across the southern UK, possibly in response to increasing temperatures, physical disturbance and reduced competition. However, little is known about S. polyschides with regard to ecological functioning and population dynamics across its geographical range. Here we examined the population demography of S. polyschides populations in southwest UK, located within the species’ range centre, to address a regional knowledge gap and to provide a baseline against which to detect future changes.

Methods

Intertidal surveys were conducted during spring low tides at three sites along a gradient of wave exposure in Plymouth Sound (Western English Channel) over a period of 15 months. Density, cover, age, biomass and morphology of S. polyschides were quantified. Additionally, less frequent sampling of shallow subtidal reefs was conducted to compare intertidal and subtidal populations.

Key Results

We recorded pronounced seasonality, with fairly consistent demographic patterns across sites and depths. By late summer, S. polyschides was a dominant habitat-former on both intertidal and subtidal reefs, with maximum standing stock exceeding 13 000 g wet weight m−2.

Conclusions

Saccorhiza polyschides is a conspicuous and abundant member of rocky reef assemblages in the region, providing complex and abundant biogenic habitat for associated organisms and high rates of primary productivity. However, its short-lived pseudo-annual life strategy is in stark contrast to dominant long-lived perennial laminarian kelps. As such, any replacement or reconfiguration of habitat-forming macroalgae due to ocean warming will probably have implications for local biodiversity and community composition. More broadly, our study demonstrates the importance of high-resolution cross-habitat surveys to generate robust baselines of kelp population demography, against which the ecological impacts of climate change and other stressors can be reliably detected.
Validity assessment in Eastern Europe: cross-validation of the Dot Counting Test and MODEMM against the TOMM-1 and Rey-15 in a Romanian mixed clinical sample
Authors: Crișan Iulia , Sava Florin Alin
Published: November 2023

Objective

This study investigated performance validity in the understudied Romanian clinical population by exploring classification accuracies of the Dot Counting Test (DCT) and the first Romanian performance validity test (PVT) (Memory of Objects and Digits and Evaluation of Memory Malingering/MODEMM) in a heterogeneous clinical sample.

Methods

We evaluated 54 outpatients (26 females; MAge = 62.02; SDAge = 12.3; MEducation = 2.41, SDEducation = 2.82) with the Test of Memory Malingering 1 (TOMM-1), Rey Fifteen Items Test (Rey-15) (free recall and recognition trials), DCT, MODEMM, and MMSE/MoCA as part of their neuropsychological assessment. Accuracy parameters and base failure rates were computed for the DCT and MODEMM indicators against the TOMM-1 and Rey-15. Two patient groups were constructed according to psychometrically defined credible/noncredible performance (i.e., pass/fail both TOMM-1 and Rey-15).

Results

Similar to other cultures, a cutoff of ≥18 on the DCT E score produced the best combination between sensitivity (0.50–0.57) and specificity (≥0.90). MODEMM indicators based on recognition accuracy, inconsistencies, and inclusion false positives generated 0.75–0.86 sensitivities at ≥0.90 specificities. Multivariable models of MODEMM indicators reached perfect sensitivities at ≥0.90 specificities against two PVTs. Patients who failed the TOMM-1 and Rey-15 were significantly more likely to fail the DCT and MODEMM than patients who passed both PVTs.

Conclusions

Our results offer proof of concept for the DCT’s cross-cultural validity and the applicability of the MODEMM on Romanian clinical examinees, further recommending the use of heterogeneous validity indicators in clinical assessments.
Generalized kernel two-sample tests
Authors: Song Hoseung , Chen Hao
Published: November 2023

Kernel two-sample tests have been widely used for multivariate data to test equality of distributions. However, existing tests based on mapping distributions into a reproducing kernel Hilbert space mainly target specific alternatives and do not work well for some scenarios when the dimension of the data is moderate to high due to the curse of dimensionality. We propose a new test statistic that makes use of a common pattern under moderate and high dimensions and achieves substantial power improvements over existing kernel two-sample tests for a wide range of alternatives. We also propose alternative testing procedures that maintain high power with low computational cost, offering easy off-the-shelf tools for large datasets. The new approaches are compared to other state-of-the-art tests under various settings and show good performance. We showcase the new approaches through two applications: the comparison of musks and nonmusks using the shape of molecules, and the comparison of taxi trips starting from John F. Kennedy airport in consecutive months. All proposed methods are implemented in an R package kerTests.
Crowdsourcing temporal transcriptomic coronavirus host infection data: Resources, guide, and novel insights
Authors: Flynn James , Ahmadi Mehdi M , McFarland Chase T , Kubal Michael D , Taylor Mark A , Cheng Zhang , Torchia Enrique C , Edwards Michael G
Published: November 2023

The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) reawakened the need to rapidly understand the molecular etiologies, pandemic potential, and prospective treatments of infectious agents. The lack of existing data on SARS-CoV-2 hampered early attempts to treat severe forms of coronavirus disease-2019 (COVID-19) during the pandemic. This study coupled existing transcriptomic data from severe acute respiratory syndrome-related coronavirus 1 (SARS-CoV-1) lung infection animal studies with crowdsourcing statistical approaches to derive temporal meta-signatures of host responses during early viral accumulation and subsequent clearance stages. Unsupervised and supervised machine learning approaches identified top dysregulated genes and potential biomarkers (e.g. CXCL10, BEX2, and ADM). Temporal meta-signatures revealed distinct gene expression programs with biological implications to a series of host responses underlying sustained Cxcl10 expression and Stat signaling. Cell cycle switched from G1/G0 phase genes, early in infection, to a G2/M gene signature during late infection that correlated with the enrichment of DNA damage response and repair genes. The SARS-CoV-1 meta-signatures were shown to closely emulate human SARS-CoV-2 host responses from emerging RNAseq, single cell, and proteomics data with early monocyte-macrophage activation followed by lymphocyte proliferation. The circulatory hormone adrenomedullin was observed as maximally elevated in elderly patients who died from COVID-19. Stage-specific correlations to compounds with potential to treat COVID-19 and future coronavirus infections were in part validated by a subset of twenty-four that are in clinical trials to treat COVID-19. This study represents a roadmap to leverage existing data in the public domain to derive novel molecular and biological insights and potential treatments to emerging human pathogens.
The ERA Registry Annual Report 2021: a summary
Authors: Boerstra Brittany A , Boenink Rianne , Astley Megan E , Bonthuis Marjolein , Abd ElHafeez Samar , Arribas Monzón Federico , Åsberg Anders , Beckerman Pazit , Bell Samira , Cases Amenós Aleix , Castro de la Nuez Pablo , ten Dam Marc A G J , Debska-Slizien Alicja , Gjorgjievski Nikola , Guidotti Rebecca , Helve Jaakko , Hommel Kristine , Idrizi Alma , Indriðason Ólafur S , Jarraya Faiçal , Kerschbaum Julia , Komissarov Kirill S , Kozliuk Nadiia , Kravljaca Milica , Lassalle Mathilde , De Meester Johan M , Ots-Rosenberg Mai , Plummer Zoe , Radunovic Danilo , Razvazhaieva Olena , Resic Halima , Rodríguez Arévalo Olga Lucía , Santiuste de Pablos Carmen , Seyahi Nurhan , Slon-Roblero María Fernanda , Stendahl Maria , Tolaj-Avdiu Miloreta , Trujillo-Alemán Sara , Ziedina Ieva , Ziginskiene Edita , Ortiz Alberto , Jager Kitty J , Stel Vianda S , Kramer Anneke
Published: November 2023

Background

The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities.

Methods

Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated.

Result

In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012–2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft.
Eosinophils in obesity and obesity-associated disorders
Authors: Hu Yanan , Chakarov Svetoslav
Published: November 2023

Despite the rising prevalence and costs for the society, obesity etiology, and its precise cellular and molecular mechanisms are still insufficiently understood. The excessive accumulation of fat by adipocytes plays a key role in obesity progression and has many repercussions on total body physiology. In recent years the immune system as a gatekeeper of adipose tissue homeostasis has been evidenced and has become a focal point of research. Herein we focus on eosinophils, an important component of type 2 immunity, assuming fundamental, yet ill-defined, roles in the genesis, and progression of obesity and related metabolic disorders. We summarize eosinophilopoiesis and eosinophils recruitment into adipose tissue and discuss how the adipose tissue environments shape their function and vice versa. Finally, we also detail how obesity transforms the local eosinophil niche. Understanding eosinophil crosstalk with the diverse cell types within the adipose tissue environment will allow us to framework the therapeutic potential of eosinophils in obesity.
Microvascular dysfunction following deferred stenting strategy in ST-segment elevation myocardial infarction: a case report
Authors: Albistur Sebastian , Torrado Juan , Niell Nicolás , Mila Rafael
Published: November 2023

Background

ST-segment elevation myocardial infarction (STEMI) has traditionally been managed with immediate reperfusion of the culprit artery, primarily through percutaneous coronary intervention and stent placement. Emerging data are highlighting the crucial importance of post-infarct microcirculatory function assessment.

Case summary

This report presents a patient with an inferior STEMI who was successfully reperfused without stent implantation. Tools such as optical coherence tomography, fractional flow reserve, and positron emission tomography computed tomography N-13 ammonia were utilized, offering comprehensive insights into the anatomical and functional characteristics of both the epicardial vessel and microcirculation.

Discussion

The recovery of the reversible component of microcirculatory dysfunction, observable as early as 5 days post-infarction, might carry significant implications for clinical decision-making. Such insights can potentially influence contemporary treatment strategies, including the consideration of deferred stenting. This case underscores the significance of post-infarct microcirculatory function and its potential impact on therapeutic approaches.
Feasibility and accuracy of real-time 3D-holographic graft length measurements
Authors: Tsai Tsung-Ying , Kageyama Shigetaka , He XingQiang , Pompilio Giulio , Andreini Daniele , Pontone Gianluca , La Meir Mark , De Mey Johan , Tanaka Kaoru , Doenst Torsten , Puskas John , Teichgräber Ulf , Schneider Ulrich , Gupta Himanshu , Leipsic Jonathon , Garg Scot , C. Revaiah Pruthvi , Stanuch Maciej , Skalski Andrzej , Onuma Yoshinobu , Serruys Patrick W
Published: November 2023

Aims

Mixed reality (MR) holograms can display high-definition images while preserving the user’s situational awareness. New MR software can measure 3D objects with gestures and voice commands; however, these measurements have not been validated. We aimed to assess the feasibility and accuracy of using 3D holograms for measuring the length of coronary artery bypass grafts.

Methods and results

An independent core lab analyzed follow-up computer tomography coronary angiograms performed 30 days after coronary artery bypass grafting in 30 consecutive cases enrolled in the FASTTRACK CABG trial. Two analysts, blinded to clinical information, performed holographic reconstruction and measurements using the CarnaLife Holo software (Medapp, Krakow, Poland). Inter-observer agreement was assessed in the first 20 cases. Another analyst performed the validation measurements using the CardIQ W8 CT system (GE Healthcare, Milwaukee, Wisconsin). Seventy grafts (30 left internal mammary artery grafts, 31 saphenous vein grafts, and 9 right internal mammary artery grafts) were measured. Holographic measurements were feasible in 97.1% of grafts and took 3 minutes 36 s ± 50.74 s per case. There was an excellent inter-observer agreement [interclass correlation coefficient (ICC) 0.99 (0.97–0.99)]. There was no significant difference between the total graft length on hologram and CT [187.5 mm (157.7–211.4) vs. 183.1 mm (156.8–206.1), P = 0.50], respectively. Hologram and CT measurements are highly correlated (r = 0.97, P < 0.001) with an excellent agreement [ICC 0.98 (0.97–0.99)].

Conclusion

Real-time holographic measurements are feasible, quick, and accurate even for tortuous bypass grafts. This new methodology can empower clinicians to visualize and measure 3D images by themselves and may provide insights for procedural strategy.
Impact of appropriateness in clinical practice: data from a single-centre nuclear cardiology laboratory
Authors: Liga Riccardo , Grassini Dario , Giorgetti Assuero , Grasso Enrico , Dalmiani Stefano , Gimelli Alessia
Published: November 2023

Aims

To verify the level of appropriateness of referral to our nuclear cardiology laboratory for stress myocardial perfusion imaging (MPI) and explore the correlation between test appropriateness patterns and ischaemia.

Methods and results

In 1870 consecutive patients (mean age 73 ± 12 years; 33% female) undergoing MPI, the level of imaging test appropriateness was evaluated according to the 2023 Appropriate Use Criteria (AUC) and the current European Society of Cardiology (ESC) guidelines for the management of chronic coronary syndromes. The evidence of moderate-to-severe ischaemia (i.e. summed difference score >7) was recorded. According to the AUC criteria, the MPI of 1638 (88%), 130 (7%), and 102 (5%) patients could be classified as ‘appropriate’, ‘inappropriate’, and ‘uncertain’, respectively. Similarly, in 1685 (90%) patients, the referral to MPI was adherent to ESC guidelines, while in 185 (10%), it was not. The majority of appropriate MPI tests showed the presence of moderate-to-severe ischaemia (55%), while only a limited number (10%; P < 0.05) of MPI tests with uncertain clinical appropriateness or clearly inappropriate indications did not. In patients managed adherently to ESC guidelines, invasive coronary angiography more frequently showed obstructive coronary artery disease (CAD) (93 vs. 47%, P < 0.001) and led to coronary revascularization (65 vs. 23%, P < 0.001) compared with patients managed non-adherently.

Conclusion

In a single-centre, single-national, single-modality population, the current rate of appropriate MPI tests is high. Appropriate referrals are associated with a higher probability of moderate-to-severe ischaemia and better downstream resource utilization than inappropriate ones.
Therapeutic management of congenital forms of endocrine hypertension
Authors: Charoensri Suranut , Auchus Richard J
Published: November 2023

Congenital forms of endocrine hypertension are rare and potentially life-threatening disorders, primarily caused by genetic defects affecting adrenal steroid synthesis and activation pathways. These conditions exhibit diverse clinical manifestations, which can be distinguished by their unique molecular mechanisms and steroid profiles. Timely diagnosis and customized management approach are crucial to mitigate unfavorable outcomes associated with uncontrolled hypertension and other related conditions. Treatment options for these disorders depend on the distinct underlying pathophysiology, which involves specific pharmacological therapies or surgical adrenalectomy in some instances. This review article summarizes the current state of knowledge on the therapeutic management of congenital forms of endocrine hypertension, focusing on familial hyperaldosteronism (FH), congenital adrenal hyperplasia, apparent mineralocorticoid excess, and Liddle syndrome. We provide an overview of the genetic and molecular pathogenesis underlying each disorder, describe the clinical features, and discuss the various therapeutic approaches available and their risk of adverse effects, aiming to improve outcomes in patients with these rare and complex conditions.
Environment predicts the maintenance of reproductive isolation in a mosaic hybrid zone of rubber rabbitbrush
Authors: Faske Trevor M , Agneray Alison C , Jahner Joshua P , Osuna-Mascaró Carolina , Sheta Lana M , Richardson Bryce A , Leger Elizabeth A , Parchman Thomas L
Published: November 2023

Widely distributed plants of western North America experience divergent selection across environmental gradients, have complex histories shaped by biogeographic barriers and distributional shifts and often illustrate continuums of reproductive isolation. Rubber rabbitbrush (Ericameria nauseosa) is a foundational shrub species that occurs across diverse environments of western North America. Its remarkable phenotypic diversity is currently ascribed to two subspecies—Ericameria nauseosa nauseosa and Ericameria nauseosa consimilis—and 22 named varieties. To understand how genetic variation is partitioned across subspecies, varieties, and environments, we used high throughput sequencing of reduced representation libraries. We found clear evidence for divergence between the two subspecies, despite largely sympatric distributions. Numerous locations exhibiting admixed ancestry were not geographically localized but were widely distributed across a mosaic hybrid zone. The occurrence of hybrid and subspecific ancestries was strongly predicted by environmental variables as well as the proximity to major ecotones between ecoregions. Although this repeatability illustrates the importance of environmental factors in shaping reproductive isolation, variability in the prevalence of hybridization also indicates these factors likely differ across ecological contexts. There was mixed evidence for the evolutionary cohesiveness of varieties, but several genetically distinct and narrow endemic varieties exhibited admixed subspecific ancestries, hinting at the possibility for transgressive hybridization to contribute to phenotypic novelty and the colonization of new environments in E. nauseosa.
Enterococcus faecium R-026 combined with Bacillus subtilis R-179 alleviate hypercholesterolemia and modulate the gut microbiota in C57BL/6 mice
Authors: Huang Jinli , Xu Yafang , Wang Minghao , Yu Shu , Li Yixuan , Tian Haoxin , Zhang Caihua , Li Huajun
Published: November 2023

Probiotics have been demonstrated to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in individuals with mild hypercholesterolemia. Our previous study found that intervention with Bacillus subtilis R-179 and Enterococcus faecium R-026, well-known probiotics, improved obesity-associated dyslipidemia through ameliorating the gut microbiota, but similar studies on hypercholesterolemia have not been reported to date. Here, we investigated the therapeutic effect of live combined B. subtilis R-179 and E. faecium R-026 (LCBE) in a C57BL/6 mouse model of hypercholesterolemia. A total of 40 mice were administered with a high-cholesterol diet (containing 1.2% cholesterol) to establish a state of hypercholesterolemia for 4 weeks. Then, mice were divided into one model group (group M) and three treatment groups (n = 10 per group), which were administered with LCBE at 0.023 g/mouse/day (group L) or 0.230 g/mouse/day (group H), or atorvastatin 0.010 g/kg/day (group A), for 5 weeks while on a high-cholesterol diet. LCBE at high doses significantly alleviated the symptoms of group M and reduced serum TC, LDL-C, and lipopolysaccharide (LPS). LCBE improved liver steatosis and adipocyte enlargement caused by a high-cholesterol diet. In addition, the administration of LCBE regulated the change in gut microbiota and diversity (Shannon index). Compared with group M, the relative abundance of Actinobacteriota, Colidextribacter, and Dubosiella dramatically decreased in the treatment groups, which were positively correlated with serum TC and LPS. These findings indicated that the mechanism of action of LCBE in treating hypercholesterolemia may be modulation of the gut microbiota. In conclusion, LCBE ameliorated lipid accumulation, reduced inflammation, and alleviated the gut microbiota imbalance in hypercholesterolemic mice. These findings support the probiotic role of LCBE as a clinical candidate for the treatment of hypercholesterolemia.
Developing the improved Community Health Fund in Tanzania: was it a fair process?
Authors: Binyaruka Peter , Mtei Gemini , Maiba John , Gopinathan Unni , Dale Elina
Published: November 2023

Tanzania developed its 2016–26 health financing strategy to address existing inequities and inefficiencies in its health financing architecture. The strategy suggested the introduction of mandatory national health insurance, which requires long-term legal, interministerial and parliamentary procedures. In 2017/18, improved Community Health Fund (iCHF) was introduced to make short-term improvements in coverage and financial risk protection for the informal sector. Improvements involved purchaser–provider split, portability of services, uniformity in premium and risk pooling at the regional level. Using qualitative methods and drawing on the policy analysis triangle framework (context, content, actors and process) and criteria for procedural fairness, we examined the decision-making process around iCHF and the extent to which it met the criteria for a fair process. Data collection involved a document review and key informant interviews (n = 12). The iCHF reform was exempt from following the mandatory legislative procedures, including processes for involving the public, for policy reforms in Tanzania. The Ministry of Health, leading the process, formed a technical taskforce to review evidence, draw lessons from pilots and develop plans for implementing iCHF. The taskforce included representatives from ministries, civil society organizations and CHF implementing partners with experience in running iCHF pilots. However, beneficiaries and providers were not included in these processes. iCHF was largely informed by the evidence from pilots and literature, but the evidence to reduce administrative cost by changing the oversight role to the National Health Insurance Fund was not taken into account. Moreover, the iCHF process lacked transparency beyond its key stakeholders. The iCHF reform provided a partial solution to fragmentation in the health financing system in Tanzania by expanding the pool from the district to regional level. However, its decision-making process underscores the significance of giving greater consideration to procedural fairness in reforms guided by technical institutions, which can enhance responsiveness, legitimacy and implementation.
A Universal Heat Semigroup Characterisation of Sobolev and BV Spaces in Carnot Groups
Authors: Garofalo Nicola , Tralli Giulio
Published: November 2023

In sub-Riemannian geometry there exist, in general, no known explicit representations of the heat kernels, and these functions fail to have any symmetry whatsoever. In particular, they are not a function of the control distance, nor they are for instance spherically symmetric in any of the layers of the Lie algebra. Despite these unfavourable aspects, in this paper we establish a new heat semigroup characterisation of the Sobolev and $BV$ spaces in a Carnot group by means of an integral decoupling property of the heat kernel.
From context adaptation to context restoration: strategies, motivations, and decision rules of managing context collapse on WeChat
Authors: Li Pengxiang , Cho Hichang , Shen Cuihua , Kong Hangchen
Published: November 2023

Context collapse occurs on social media platforms when different groups are mixed into one audience. To advance the understanding of the extensive and complex coping strategies people use to address context collapse, this study makes a conceptual distinction between passively adapting by sharing context-free, general information (context adaptation) and rebuilding contexts to satisfy the diverse needs of impression management (context restoration). This study in-depth interviewed 51 WeChat users (30 working professionals and 21 college students) in urban China. The results identified strategies for context restoration through reconstructing contextual boundaries on psychological, relational, spatial, and temporal dimensions. These findings highlight individual (effort minimization, self-consciousness, and privacy concerns) and audience factors (the heterogeneity and activeness of the audience) in determining the adoption of specific strategies. This study emphasizes the subjectivity and agency of users in relation to the social media ecosystem and develops a theoretical spectrum systematically situating users’ coping behaviors for mitigating context collapse.
Improved 13C metabolic flux analysis in Escherichia coli metabolism: application of a high-resolution MS (GC–EI–QTOF) for comprehensive assessment of MS/MS fragments
Authors: Richter Chris , Grafahrend-Belau Eva , Ziegler Jörg , Raorane Manish L , Junker Björn H
Published: November 2023

Gas chromatography–tandem mass spectrometry with electron ionization (GC–EI–MS/MS) provides rich information on stable-isotope labeling for 13C-metabolic flux analysis (13C-MFA). To pave the way for the routine application of tandem MS data for metabolic flux quantification, we aimed to compile a comprehensive library of GC–EI–MS/MS fragments of tert-butyldimethylsilyl (TBDMS) derivatized proteinogenic amino acids. First, we established an analytical workflow that combines high-resolution gas chromatography-quadrupole time-of-flight mass spectrometry and fully 13C-labeled biomass to identify and structurally elucidate tandem MS amino acid fragments. Application of the high-mass accuracy MS procedure resulted into the identification of 129 validated precursor–product ion pairs of 13 amino acids with 30 fragments being accepted for 13C-MFA. The practical benefit of the novel tandem MS data was demonstrated by a proof–of–concept study, which confirmed the importance of the compiled library for high-resolution 13C-MFA.

One sentence summary

An analytical workflow that combines high-resolution mass spectrometry (MS) and fully 13C-labeled biomass to identify and structurally elucidate tandem MS amino acid fragments, which provide positional information and therefore offering significant advantages over traditional MS to improve 13C-metabolic flux analysis.
Education, epistemic justice, and truthfulness: Miranda Fricker interviewed by A. C. Nikolaidis and Winston C. Thompson
Authors: Nikolaidis A C , Thompson Winston C , Fricker Miranda
Published: November 2023

In her groundbreaking book, Epistemic Injustice, renowned moral philosopher and social epistemologist Miranda Fricker coined the term epistemic injustice to draw attention to the pervasive impact of epistemic oppression on marginalized social groups. Fricker’s account spurred a flurry of scholarship regarding the discriminatory impact of epistemic injustice and gave birth to a domain of philosophical inquiry that has extended far beyond the disciplinary boundaries of philosophy. In this interview, Fricker responds to questions posed by A. C. Nikolaidis and Winston C. Thompson that address the ways in which epistemic injustice intersects with education as a human endeavour and social institution. In doing so, Fricker reflects on her motivations in writing her book more than fifteen years ago and explicitly addresses some of the most significant contributions of the concept of epistemic injustice as a tool for analysing issues in education. She also offers insights on the purpose of education, outlines educational manifestations of epistemic injustice, and discusses the virtues that educators must exhibit and inculcate in their students in order for epistemic justice to obtain.
Controlling the false discovery rate in transformational sparsity: Split Knockoffs
Authors: Cao Yang , Sun Xinwei , Yao Yuan
Published: November 2023

Controlling the False Discovery Rate (FDR) in a variable selection procedure is critical for reproducible discoveries, and it has been extensively studied in sparse linear models. However, it remains largely open in scenarios where the sparsity constraint is not directly imposed on the parameters but on a linear transformation of the parameters to be estimated. Examples of such scenarios include total variations, wavelet transforms, fused LASSO, and trend filtering. In this paper, we propose a data-adaptive FDR control method, called the Split Knockoff method, for this transformational sparsity setting. The proposed method exploits both variable and data splitting. The linear transformation constraint is relaxed to its Euclidean proximity in a lifted parameter space, which yields an orthogonal design that enables the orthogonal Split Knockoff construction. To overcome the challenge that exchangeability fails due to the heterogeneous noise brought by the transformation, new inverse supermartingale structures are developed via data splitting for provable FDR control without sacrificing power. Simulation experiments demonstrate that the proposed methodology achieves the desired FDR and power. We also provide an application to Alzheimer’s Disease study, where atrophy brain regions and their abnormal connections can be discovered based on a structural Magnetic Resonance Imaging dataset.
Adaptive bootstrap tests for composite null hypotheses in the mediation pathway analysis
Authors: He Yinqiu , Song Peter X K , Xu Gongjun
Published: November 2023

Mediation analysis aims to assess if, and how, a certain exposure influences an outcome of interest through intermediate variables. This problem has recently gained a surge of attention due to the tremendous need for such analyses in scientific fields. Testing for the mediation effect (ME) is greatly challenged by the fact that the underlying null hypothesis (i.e. the absence of MEs) is composite. Most existing mediation tests are overly conservative and thus underpowered. To overcome this significant methodological hurdle, we develop an adaptive bootstrap testing framework that can accommodate different types of composite null hypotheses in the mediation pathway analysis. Applied to the product of coefficients test and the joint significance test, our adaptive testing procedures provide type I error control under the composite null, resulting in much improved statistical power compared to existing tests. Both theoretical properties and numerical examples of the proposed methodology are discussed.
An intronic RNA element modulates Factor VIII exon-16 splicing
Authors: Tse Victor , Chacaltana Guillermo , Gutierrez Martin , Forino Nicholas M , Jimenez Arcelia G , Tao Hanzhang , Do Phong H , Oh Catherine , Chary Priyanka , Quesada Isabel , Hamrick Antonia , Lee Sophie , Stone Michael D , Sanford Jeremy R
Published: November 2023

Pathogenic variants in the human Factor VIII (F8) gene cause Hemophilia A (HA). Here, we investigated the impact of 97 HA-causing single-nucleotide variants on the splicing of 11 exons from F8. For the majority of F8 exons, splicing was insensitive to the presence of HA-causing variants. However, splicing of several exons, including exon-16, was impacted by variants predicted to alter exonic splicing regulatory sequences. Using exon-16 as a model, we investigated the structure–function relationship of HA-causing variants on splicing. Intriguingly, RNA chemical probing analyses revealed a three-way junction structure at the 3′-end of intron-15 (TWJ-3–15) capable of sequestering the polypyrimidine tract. We discovered antisense oligonucleotides (ASOs) targeting TWJ-3–15 partially rescue splicing-deficient exon-16 variants by increasing accessibility of the polypyrimidine tract. The apical stem loop region of TWJ-3–15 also contains two hnRNPA1-dependent intronic splicing silencers (ISSs). ASOs blocking these ISSs also partially rescued splicing. When used in combination, ASOs targeting both the ISSs and the region sequestering the polypyrimidine tract, fully rescue pre-mRNA splicing of multiple HA-linked variants of exon-16. Together, our data reveal a putative RNA structure that sensitizes F8 exon-16 to aberrant splicing.
RefSeq and the prokaryotic genome annotation pipeline in the age of metagenomes
Authors: Haft Daniel H , Badretdin Azat , Coulouris George , DiCuccio Michael , Durkin A Scott , Jovenitti Eric , Li Wenjun , Mersha Megdelawit , O’Neill Kathleen R , Virothaisakun Joel , Thibaud-Nissen Françoise
Published: November 2023

The Reference Sequence (RefSeq) project at the National Center for Biotechnology Information (NCBI) contains over 315 000 bacterial and archaeal genomes and 236 million proteins with up-to-date and consistent annotation. In the past 3 years, we have expanded the diversity of the RefSeq collection by including the best quality metagenome-assembled genomes (MAGs) submitted to INSDC (DDBJ, ENA and GenBank), while maintaining its quality by adding validation checks. Assemblies are now more stringently evaluated for contamination and for completeness of annotation prior to acceptance into RefSeq. MAGs now account for over 17000 assemblies in RefSeq, split over 165 orders and 362 families. Changes in the Prokaryotic Genome Annotation Pipeline (PGAP), which is used to annotate nearly all RefSeq assemblies include better detection of protein-coding genes. Nearly 83% of RefSeq proteins are now named by a curated Protein Family Model, a 4.7% increase in the past three years ago. In addition to literature citations, Enzyme Commission numbers, and gene symbols, Gene Ontology terms are now assigned to 48% of RefSeq proteins, allowing for easier multi-genome comparison. RefSeq is found at https://www.ncbi.nlm.nih.gov/refseq/. PGAP is available as a stand-alone tool able to produce GenBank-ready files at https://github.com/ncbi/pgap.
A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex
Authors: Jandrey Elisa Helena Farias , Barnabé Gabriela Filoso , Maldaun Marcos , Asprino Paula Fontes , dos Santos Natália Cristina , Inoue Lilian Tiemi , Rozanski Andrei , Galante Pedro Alexandre Favoretto , Marie Suely Kazue Nagahashi , Oba-Shinjo Sueli Mieko , dos Santos Tiago Góss , Chammas Roger , Lancellotti Carmen Lucia Penteado , Furnari Frank B , Camargo Anamaria Aranha , Costa Érico Tosoni
Published: November 2023

Background

Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.

Methods

We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma’s growth and motility.

Results

ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces γ-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-β and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs.

Conclusions

Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.
Potato virus Y viral protein 6K1 inhibits the interaction between defense proteins during virus infection
Authors: Fang Le , Geng Chao , Wei Xin-Yu , Dong Chen-Chen , Pang Ju-Ping , Yan Zhi-Yong , Jiang Jun , Tian Yan-Ping , Li Xiang-Dong
Published: November 2023

14-3-3 proteins play vital roles in plant defense against various pathogen invasions. To date, how 14-3-3 affects virus infections in plants remains largely unclear. In this study, we found that Nicotiana benthamiana 14-3-3h interacts with TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (TCTP), a susceptibility factor of potato virus Y (PVY). Silencing of Nb14-3-3h facilitates PVY accumulation, whereas overexpression of Nb14-3-3h inhibits PVY replication. The antiviral activities of 3 Nb14-3-3h dimerization defective mutants are significantly decreased, indicating that dimerization of Nb14-3-3h is indispensable for restricting PVY infection. Our results also showed that the mutant Nb14-3-3hE16A, which is capable of dimerizing but not interacting with NbTCTP, has reduced anti-PVY activity; the mutant NbTCTPI65A, which is unable to interact with Nb14-3-3h, facilitates PVY replication compared with the wild-type NbTCTP, indicating that dimeric Nb14-3-3h restricts PVY infection by interacting with NbTCTP and preventing its proviral function. As a counter-defense, PVY 6K1 interferes with the interaction between Nb14-3-3h and NbTCTP by competitively binding to Nb14-3-3h and rescues NbTCTP to promote PVY infection. Our results provide insights into the arms race between plants and potyviruses.
LHT1/MAC7 contributes to proper alternative splicing under long-term heat stress and mediates variation in the heat tolerance of Arabidopsis
Authors: Isono Kazuho , Nakamura Kotaro , Hanada Kousuke , Shirai Kazumasa , Ueki Mao , Tanaka Keisuke , Tsuchimatsu Takashi , Iuchi Satoshi , Kobayashi Masatomo , Yotsui Izumi , Sakata Yoichi , Taji Teruaki
Published: November 2023

Natural genetic variation has facilitated the identification of genes underlying complex traits such as stress tolerances. We here evaluated the long-term (L-) heat tolerance (37°C for 5 days) of 174 Arabidopsis thaliana accessions and short-term (S-) heat tolerance (42°C, 50 min) of 88 accessions and found extensive variation, respectively. Interestingly, L-heat–tolerant accessions are not necessarily S-heat tolerant, suggesting that the tolerance mechanisms are different. To elucidate the mechanisms underlying the variation, we performed a chromosomal mapping using the F2 progeny of a cross between Ms-0 (a hypersensitive accession) and Col-0 (a tolerant accession) and found a single locus responsible for the difference in L-heat tolerance between them, which we named Long-term Heat Tolerance 1 (LHT1). LHT1 is identical to MAC7, which encodes a putative RNA helicase involved in mRNA splicing as a component of the MOS4 complex. We found one amino acid deletion in LHT1 of Ms-0 that causes a loss of function. Arabidopsis mutants of other core components of the MOS4 complex—mos4-2, cdc5-1, mac3a mac3b, and prl1 prl2—also showed hypersensitivity to L-heat stress, suggesting that the MOS4 complex plays an important role in L-heat stress responses. L-heat stress induced mRNA processing–related genes and compromised alternative splicing. Loss of LHT1 function caused genome-wide detrimental splicing events, which are thought to produce nonfunctional mRNAs that include retained introns under L-heat stress. These findings suggest that maintaining proper alternative splicing under L-heat stress is important in the heat tolerance of A. thaliana.
Effect of covariate shift on multi-class classification of Fermi-LAT sources
Authors: Malyshev Dmitry V
Published: November 2023

Probabilistic classification of unassociated Fermi-LAT sources using machine learning methods has an implicit assumption that the distributions of associated and unassociated sources are the same as a function of source parameters, which is not the case for the Fermi-LAT catalogues. The problem of different distributions of training and testing (or target) data sets as a function of input features (covariates) is known as the covariate shift. In this paper, we, for the first time, quantitatively estimate the effect of the covariate shift on the multi-class classification of Fermi-LAT sources. We introduce sample weights proportional to the ratio of unassociated to associated source probability density functions so that associated sources in areas, which are densely populated with unassociated sources, have more weight than the sources in areas with few unassociated sources. We find that the covariate shift has relatively little effect on the predicted probabilities, i.e. the training can be performed either with weighted or with unweighted samples, which is generally expected for the covariate shift problems. The main effect of the covariate shift is on the estimated performance of the classification. Depending on the class, the covariate shift can lead up to 10–20 per cent reduction in precision and recall compared with the estimates, where the covariate shift is not taken into account.