bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Global talent’ or ‘labour migrant’?—Discursive noise and the strategic organization of difference in the competition state
Authors: Martel Kerstin
Published: January 2025

This article explores how migrant categorizations are (re)produced across distinct discursive terrains in public spheres and in the academic fields of migration studies and management and organization studies. It illustrates state-economy entanglements through the emergence of novel migrant labels, such as ‘global talent’, within the empirical context of Copenhagen, Denmark, and at a European scale. The findings suggest that the use and enactment of distinct categorizations in public discourse organizes social difference strategically: performative speech acts ascribe symbolic capital and status to foreign newcomers who are of economic value to the nation state, while not granting this privilege to others. Thereby, the ideological and discursive infusion of a human capital rationale into the state’s migration regime and at supra-national instances supports not only processes of Othering, but produces ontological effects. The use of certain designations in specific situations, such as ‘global talent’ in a mayor’s welcome address or ‘expat’ in housing adverts, seems inappropriate and unsettling. To grasp the fragmentation, accumulation and disturbing repetition of labels across distinct discursive spheres, the author introduces the concept of ‘discursive noise’. The denser the discursive assemblage becomes, and the more congruent categorizations across distinct spheres seem to be, the less perceptible underlying ambiguities are. The idea of discursive noise upholds that the repetition and circulation of consistent, yet conceptually incoherent migrant designations across commercial and political spheres is deliberate and strategically intended. Discursive noise conceals ideological underpinnings of migrant triage whilst backing politico-economic goals of the competition state.
Gaussian process regression of temperature-dependent radial velocities
Authors: Rescigno Federica , Al Moulla Khaled
Published: January 2025

Gaussian processes (GPs) described by quasi-periodic covariance functions have in recent years become a widely used tool to model the impact of stellar activity on radial velocity (RV) measurements. We perform a GP regression analysis on solar RV time series measured from spectral segments formed at different temperatures within the photosphere in order to evaluate the relation between the best-fit GP kernel hyperparameters and the observed activity signal as a function of temperature. The posterior distributions of the hyperparameters show subtle differences between high- and low-activity phases and as a function of the spectral formation temperature range, which could have implications on the characteristics of the activity signal and its optimal modelling. For the temperature-dependent RVs, we find that at high and low activity alike, the minimal RV dispersion is obtained at intermediately cool temperature ranges ($4000{-}4750 \,{\rm K}$), for both the observed and GP model-subtracted RVs. Finally, we compare and correlate our temperature-dependent RVs with RV components derived from disc-resolved Dopplergrams of the Sun, for which we find a consistently strong correlation between RVs related to hotter temperature ranges and the dominant RV component due to the inhibition of convection.
Expanding molecular shell and possible γ-ray source associated with supernova remnant kesteven 67
Authors: Shen Yun-Zhi , Chen Yang , Zhang Xiao , Tu Tian-Yu , Zhong Wen-Juan , Zhang Qian-Qian , Liu Qian-Cheng
Published: January 2025

We investigate the molecular environment of the supernova remnant  (SNR) Kesteven 67 (G18.8+0.3) using observations in $^{12}$CO, $^{13}$CO, HCO$^+$, and HCN lines and possible associated $\gamma$-ray emission using 16-yr Fermi–LAT observation. We find that the SNR is closely surrounded by a molecular belt in the southeastern boundary, with the both recessed in the band-like molecular gas structure along the Galactic plane. The asymmetric molecular line profiles are widely present in the surrounding gas around local-standard-of-rest velocity $+20\, {\mathrm{k}\mathrm{ m}}\, {\mathrm{s}}^{-1}$. The secondary components centred at $\sim +16\, {\mathrm{k}\mathrm{ m}}\, {\mathrm{s}}^{-1}$ in the belt and $\sim +26\, {\mathrm{k}\mathrm{ m}}\, {\mathrm{s}}^{-1}$ in the northern clump can be ascribed to the motion of a wind-blown molecular shell. This explanation is supported by the position–velocity diagram along a line cutting across the remnant, which shows an arc-like pattern, suggesting an expanding gas structure. With the simulation of chemical effects of shock propagation, the abundance ratios N(HCO$^+$)/N($^{12}$CO) $\sim 2.6\times 10^{-5}$–$3.6\times 10^{-4}$ obtained in the belt can be more naturally interpreted by the wind-driven bubble shock than by the SNR shock. The belt and northern clump are very likely to be parts of an incomplete molecular shell of bubble driven by O-type progenitor star’s wind. The analysis of 0.2–500 GeV $\gamma$-ray emission uncovers a possible point source (‘Source A’) about 6.5$\sigma$ located in the north of the SNR, which essentially corresponds to northern molecular clump. Our spectral fit of the emission indicates that a hadronic origin is favoured by the measured Galactic number ratio between CR electrons and protons $\sim 0.01$.
Genome-wide CRISPR-Cas9 screens identify BCL family members as modulators of response to regorafenib in experimental glioma
Authors: Haeusser Lara Annina , Becker Hannes , Kuhlburger Laurence , Zago Marcello , Walter Bianca , Tsiami Foteini , Erdmann Sarah , Trampert Jil , Surender Surender , Stahl Aaron , Templin Markus , Wegner Eileen , Schmidt Tobias , Schmees Christian , Casadei Nicolas , Sevenich Lisa , Claassen Manfred , Nahnsen Sven , Beck Susanne , Merk Daniel Josef , Tabatabai Ghazaleh
Published: January 2025

Background

Registered systemic treatment options for glioblastoma patients are limited. The phase II REGOMA trial suggested an improvement of median overall survival in progressive glioblastoma by the multi-tyrosine kinase inhibitor regorafenib. This has not been confirmed by GBM AGILE. So far, regorafenib has been administered as monotherapy or as an addition to standard of care in newly diagnosed glioblastoma. Rational combination therapies involving regorafenib might be a reasonable strategy. Here, we aimed at identifying functionally instructed combination therapies involving regorafenib.

Methods

We applied a genome-wide CRISPR-Cas9-based functional genomics target discovery approach using activation and knockout screens followed by genetic, pharmacological, functional validations. Regorafenib-induced molecular alterations were assessed by RNA sequencing and DigiWest. We investigated selected functionally instructed combination therapies in three orthotopic glioma mouse models in vivo (syngeneic SMA560/VM/Dk model and two xenograft models) and performed immunohistochemistry of post-treatment brains.

Results

We identified potential modifiers of regorafenib response, including BCL2, BCL2L1, ITGB3, FOXC1, SERAC1, ARAF, and PLCE1. The combination of regorafenib with Bcl-2/Bcl-xL inhibition was superior to both monotherapies alone in vitro, ex vivo, and in vivo. We identified regorafenib-induced regulations of the Bcl-2 downstream target chemokine receptor 1 (CCR1) as one potential underlying molecular mediator. Furthermore, regorafenib led to changes in the myeloid compartment of the glioma-associated microenvironment.

Conclusions

This preclinical study uses a functional genomics-based target discovery approach with subsequent validations involving regorafenib. It serves as a biological rationale for clinical translation. Particularly, an investigation of the combination of regorafenib plus navitoclax within a clinical trial is warranted.
The Display and Advertising of Roll-Your-Own Tobacco at Points-of-Sale in Argentina, Guatemala, Mexico, and Peru
Authors: Elicabe Emilia , Arnaudo María Belén , Moodie Crawford , Best Catherine , Alexandrou Georgia , Mejia Raúl
Published: January 2025

Introduction

While roll-your-own (RYO) tobacco consumption is highest in Europe, increased sales are reported in Latin America. We are unaware of any research that explores the display and advertising of RYO tobacco in this region.

Aims and Methods

An observational study was conducted at tobacco-selling points-of-sale (POS, N = 2081) near schools in cities in Argentina, Guatemala, Mexico, and Peru between April and July 2023. In each of the 16 cities (four per country), schools were randomly selected and stratified according to neighborhood socioeconomic status, with all POS located in pre-established routes around schools observed. A codebook was used to assess the display of RYO tobacco and accessories (ie, rolling papers and filters) and the presence of advertising for these products. Logistic regressions were employed to estimate the association between the display of RYO tobacco and accessories (defined as being visible at the points-of-sale) and type of points-of-sale, neighborhood socioeconomic status, and city.

Results

Apart from a single store in Guatemala, RYO tobacco and accessories were only observed in Argentina, at 110 (21.5%) POS. In Argentina, RYO tobacco and accessories were more likely to be displayed in convenience and neighborhood stores compared to kiosks, in high and middle socioeconomic neighborhoods compared to low socioeconomic neighborhoods, and in Cordoba and Santa Rosa than in Quilmes and San Salvador de Jujuy. Advertising for RYO tobacco (1.8%) and accessories (3.1%) at POS was uncommon.

Conclusion

This study provides insight into RYO tobacco penetration in multiple Latin American countries, finding that the display of this product is largely restricted to Argentina.

Implications

Increasing sales of RYO tobacco have been reported in Latin America. Despite this, there is limited academic research on the consumption of RYO tobacco in this region and no research on its presence at the points-of-sale. This study provides insight into RYO tobacco and accessories penetration in Argentina, Guatemala, Mexico, and Peru, finding that the display of this product at points-of-sale is generally limited to Argentina. Continued monitoring of the display and marketing of this product is needed across these countries. Research in Argentina exploring how RYO tobacco and accessories are perceived by smokers and young people would be of value.
The Prevalence and Determinants of Undernutrition Among Infants and Children Aged 6 Months to 5 Years in Sub-Saharan African Countries: A Systematic Scoping Review
Authors: Riwa Francis P , Odgers-Jewell Kate , Jones Mark A , Mushi Andrew A
Published: January 2025

Objective

To explore the prevalence and determinants of undernutrition among infants and children aged 6 months to 5 years in sub-Saharan African countries.

Background

Despite substantial progress over the past 20 years, undernutrition has remained an alarming global challenge. Sub-Saharan Africa is the only region where the prevalence of stunting in children younger than 5 years has significantly increased. This study seeks to update the evidence on the prevalence and determinants of childhood undernutrition in this vulnerable region.

Methods

This systematic scoping review was conducted following the 2018 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Five electronic databases were searched on December 14, 2022, with no date or language restrictions. Primary studies presenting evidence on the prevalence and determinants of childhood undernutrition among infants and children aged 6 months to 5 years were included. Data on the prevalence of stunting, wasting, and underweight, and on determinants of undernutrition were extracted, described, and compared with national survey data.

Results

A total of 59 publications from 11 countries were included, with most studies conducted in Ethiopia (n = 38) and Tanzania (n = 7). Stunting prevalence ranged from 8% to 64%, wasting prevalence ranged from 1% to 58%, and the prevalence of underweight ranged from 2% to 63%. The most frequently reported determinants of undernutrition were the child’s age (>24 months), male sex, maternal illiteracy, diarrhea or illness in the past 2 weeks, low household socioeconomic status, or living in a larger household (n > 4 members). Overall, 56% of the included studies reported higher stunting prevalence, 60% reported higher wasting prevalence, and 57% reported a higher prevalence of underweight than reported by relevant national surveys.

Conclusion

The prevalence of childhood undernutrition reported by primary studies is often higher than that reported by national surveys. Several immediate and underlying determinants influence childhood undernutrition. Future research should incorporate the findings from primary research to develop holistic, multistrategy approaches to address childhood undernutrition in sub-Saharan African countries.
Dynamics of Persistent Submicroscopic and Microscopic Plasmodium falciparum in Pregnant Women Under Intermittent Preventive Treatment: A Study Cohort in Benin
Authors: Jafari-Guemouri Sayeh , Dégbègni Robinson , Courtois Laura , Accrombessi Manfred , Massougbodji Achille , Ding Xavier C , Ndam Nicaise Tuikue , Mama Atika , Fievet Nadine , Sarrasin-Hubert Véronique , Cottrell Gilles , Briand Valérie
Published: January 2025

Background

Malaria infections in pregnancy are a major cause of maternal morbidity and neonatal mortality in sub-Saharan Africa. A high proportion of these infections are submicroscopic, which are usually asymptomatic and therefore untreated during pregnancy. Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) aims to prevent and treat all potential infections whether submicroscopic or not. However, the resistance of parasites to SP is steadily increasing. The dynamic of microscopic and submicroscopic infections in a cohort of Beninese women throughout their pregnancy and its relation to IPTp-SP has been assessed.

Methods

As a subsample of the RECIPAL project, 130 women with at least 2 infections detected by polymerase chain reaction during their pregnancy were included. Infections were categorized as new (isolated) or persistent based on msp-2 genotyping, where persistent infections had identical genotypes in all studied time points. Submicroscopic infections were defined as polymerase chain reaction–positive and thick blood smear–negative. The persistence of infections according to IPTp-SP uptake was assessed.

Results

A total of 73.1% of women (95 women of 130) had exclusively persistent infections throughout their pregnancy, whereas only 7.7% (10 of 130) had exclusively new infections. During pregnancy, the median time spent with 1 persistent infection was 7.2 weeks. A considerable proportion of these persistent infections 64.3% (72 of 113) was only submicroscopic. Approximately 20% of these persistent infections occurred despite the use of IPTp-SP.

Conclusions

Using new antimalarial combinations could contribute to limit the persistence of submicroscopic infections and their probable negative effects on the mother and the fetus.
Phenylalanine ammonia-lyase 2 regulates secondary metabolism and confers manganese tolerance in Stylosanthes guianensis
Authors: Wang Linjie , Li Jifu , Liu Liting , Dong Rongshu , Liu Guodao , Rao Idupulapati M , Chen Zhijian
Published: January 2025

Stylo (Stylosanthes guianensis) is a tropical legume that exhibits considerable tolerance to manganese (Mn) toxicity, which severely constrains plant growth in acidic soils. To elucidate the Mn detoxification mechanisms in stylo, this study investigated the excess Mn-regulated metabolic profile of stylo roots and examined the role of metabolic enzymes in Mn tolerance. Excess Mn triggered oxidative stress in the 2 stylo genotypes tested. However, Mn-stimulated activation of antioxidant defense systems was observed in the Mn-tolerant genotype RY5 but not in the Mn-sensitive genotype TF0317. Metabolomic analysis of the Mn-tolerant RY5 roots revealed numerous excess Mn-responsive metabolites, mainly related to flavonoids and phenolic acids. Furthermore, a set of genes involved in the phenylpropanoid/flavonoid pathway were upregulated by excess Mn in stylo roots, especially in RY5. We characterized the excess Mn-inducible gene SgPAL2, encoding phenylalanine ammonia-lyase. SgPAL2 localized to the endoplasmic reticulum. Compared with control plants, SgPAL2 overexpression led to increases in shoot and root dry weights under Mn-excess conditions, whereas SgPAL2 suppression had the opposite effect. Moreover, SgPAL2 overexpression dramatically altered secondary metabolism, particularly flavonoid metabolism. In a bioassay, the inhibition of root elongation caused by excess Mn was alleviated by treatment with exogenous calycosin, an SgPAL2-regulated isoflavonoid, suggesting calycosin can detoxify Mn. Taken together, these findings indicate that SgPAL2 plays a critical role in enhancing Mn tolerance in stylo through metabolic regulation.
Wildland fire entrainment: The missing link between wildland fire and its environment
Authors: Linn Rodman R , Hiers John Kevin , O’Brien Joseph J , Yedinak Kara , Hoffman Chad , Canfield Jesse , Robinson David , Goodrick Scott
Published: January 2025

Wildfires are growing in destructive power, and accurately predicting the spread and intensity of wildland fire is essential for managing ecological and societal impacts. No current operational models used for fire behavior prediction resolve critical fire-atmospheric coupling or nonlocal influences of the fire environment, rendering them inadequate in accounting for the range of wildland fire behavior scenarios under increasingly novel fuel and climate conditions. Here, we present a new perspective on a dominant fire-atmospheric feedback mechanism, which we term wildland fire entrainment (WFE). WFE is the fluid motion associated with air movement toward the fire driven by pressure gradients created by buoyant updrafts, and through integration of nonlocal influences on fire behavior, it plays a pivotal role in predicting wildland fire spread. WFE dynamically integrates all aspects of a fire's surrounding environment, fuels, topography, winds and fire line geometry to rate and pattern of fire spread and energy release. Because WFE explicitly incorporates fire-induced buoyancy, it links recent advances in idealized combustion research to the dynamic and highly variable wildland fire environment. Incorporating WFE into emerging fire models will allow more robust predictions of fire behavior and spread.
Enhancing molecular oxygen activation by nitrogen-doped carbon encapsulating FeNi alloys with ultra-low Pt loading
Authors: Zhu Dandan , Huang Yu , Shi Xianjin , Li Rong , Wang Zhenyu , Peng Wei , Cao Junji , Lee Shuncheng
Published: January 2025

Modulating the electronic structure of noble metals via electronic metal–support interaction (EMSI) has been proven effectively for facilitating molecular oxygen activation and catalytic oxidation reactions. Nevertheless, the investigation of the fundamental mechanisms underlying activity enhancement has primarily focused on metal oxides as supports, especially in the catalytic degradation of volatile organic compounds. In this study, a novel Pt catalyst supported on nitrogen-doped carbon encapsulating FeNi alloy, featuring ultrafine Pt nanoparticles, was synthesized. This catalyst demonstrated exceptional catalytic activity (92%), recyclability, and water tolerance for the deep oxidation of formaldehyde at room temperature. Structural analyses and theoretical calculations revealed a directional electron transfer from FeNi alloy to Pt, even there is no direct contact between them. This electron penetration effect, mediated by carbon, conferred electron-rich properties to Pt, leading to the activation of molecular oxygen by elongating O–O bond length (1.405 Å). Consequently, efficient formaldehyde removal was achieved with an ultra-low Pt loading. This investigation offers a novel perspective on modulating the electronic structure of Pt by engineering a unique EMSI effect between a nonoxide support and active species, thereby enabling efficient oxygen activation for air purification.
Mitochondria-targeting Nanomedicines with Autophagy Inhibitor to Enhance Cancer Photothermal-Chemotherapy
Authors: Chen Shuqi , Gao Wenxia , Chang Shuhua , He Bin , Zhang Congbo , Liu Miaochang , Ye Xueting
Published: January 2025

In this paper, we fabricated nanomedicines with mitochondrial targeting function and autophagy inhibitor for enhancing cancer photothermal-chemotherapy. The nanoparticles were fabricated with gold nanoparticles (AuNPs) as cores and amphiphilic dextran with (3-carboxypropyl) triphenyl phosphorus bromide and β-cyclodextrin (β-CD) modification (TPP-DCD) as shells, the chemotherapeutic doxorubicin (DOX) and autophagy inhibitor chloroquine (CQ) were encapsulated in the nanoparticles. The TPP-DCD was synthesized via the immobilization of 2-aminoethanethiol modified β-CD and (3-carboxypropyl) triphenylphosphonium bromide on dextran to receive coordination interaction with AuNPs and mitochondria targeting. The size, morphology, and properties of the Au@DOX/CQ@TPP-DCD nanoparticles were studied. The nanomedicines efficiently targeted cellular mitochondria to produce reactive oxygen species (ROS) and photothermal effect under NIR irradiation. The released DOX and CQ could not only kill tumor cells directly but also inhibit the autophagy of cancer cells to enhance therapeutic effects. Both in vitro and in vivo anticancer activities of the nanomedicines were investigated in detail. The in vivo imaging demonstrated that the Au@DOX/CQ@TPP-DCD nanomedicines exhibited efficient targeting, accumulation, and retention in tumor-bearing mice. The cancer cells apoptosis and tumor suppression were greatly accelerated with the addition of 808 nm NIR irradiation, the Au@DOX/CQ@TPP-DCD nanomedicine exhibited significant synergistic therapy as 75% tumors on mice were disappeared. The Au@DOX/CQ@TPP-DCD nanoparticle is a promising nanomedicine for cancer therapy with synergistic effects.
Seryl‐tRNA synthetase inhibits Wnt signaling and breast cancer progression and metastasis
Authors: Jiang Lei , Wang Justin , Liu Ze , Zhang Qian , Yang Xiang‐Lei
Published: January 2025

Tumors require ample protein synthesis to grow, and aminoacyl‐tRNA synthetases, as critical translation factors, are expected to support cancer progression. Unexpectedly, overexpression of seryl‐tRNA synthetase (SerRS) suppresses primary tumor growth of breast cancer. However, the effects of SerRS on metastasis have not been studied. We observe a decrease in SerRS expression in breast cancer patient metastases compared with matched primary tumors, suggesting an inhibitory role of SerRS in metastasis. Through mouse metastasis models using breast cancer cell lines overexpressing SerRS, we show that SerRS impedes not only primary tumor growth but also establishment of metastases, and the effect of SerRS on metastasis can be independent of its impact on the primary tumor. SerRS also inhibits tumor growth with induced, post‐tumor‐onset overexpression, demonstrating its potential as an anticancer therapeutic. Tumor RNA‐seq analysis identified Wnt signaling among the top SerRS‐regulated pathways. Using cell‐based studies, we confirm SerRS suppresses Wnt signaling and metastatic processes in breast cancer cells. To the best of our knowledge, this is the first study to show a component of the translation machinery can act as both a tumor and metastasis suppressor.
Hsf1 is essential for proteotoxic stress response in smyd1b‐deficient embryos and fish survival under heat shock
Authors: Xiao Huanhuan , Li Mofei , Zhong Yongwang , Patel Avani , Xu Rui , Zhang Chenyu , Athey Thomas W. , Fang Shengyun , Xu Tianjun , Du Shaojun
Published: January 2025

Molecular chaperones play critical roles in post‐translational maintenance in protein homeostasis. Previous studies have shown that loss of Smyd1b function results in defective myofibril organization and dramatic upregulation of heat shock protein gene (hsp) expression in muscle cells of zebrafish embryos. To investigate the molecular mechanisms and functional importance of this stress response, we characterized changes of gene expression in smyd1b knockdown and knockout embryos using RNA‐seq. The results showed that the top upregulated genes encode mostly cytosolic heat shock proteins. Co‐IP assay revealed that the upregulated cytosolic Hsp70s associate with myosin chaperone UNC45b which is critical for myosin protein folding and sarcomere assembly. Strikingly, several hsp70 genes also display muscle‐specific upregulation in response to heat shock‐induced stress in zebrafish embryos. To investigate the regulation of hsp gene upregulation and its functional significance in muscle cells, we generated heat shock factor 1 (hsf−/‐) knockout zebrafish mutants and analyzed hsp gene expression and muscle phenotype in the smyd1b−/−single and hsf1−/−;smyd1b−/− double‐mutant embryos. The results showed that knockout of hsf1 blocked the hsp gene upregulation and worsened the muscle defects in smyd1b−/− mutant embryos. Moreover, we demonstrated that Hsf1 is essential for fish survival under heat shock (HS) conditions. Together, these studies uncover a correlation between Smyd1b deficiency and the Hsf1‐activated heat shock response (HSR) in regulating muscle protein homeostasis and myofibril assembly and demonstrate that the Hsf1‐mediated hsp gene upregulation is vital for the survival of zebrafish larvae under thermal stress conditions.
Inhibition of ASIC1a reduces ferroptosis in rheumatoid arthritis articular chondrocytes via the p53/NRF2/SLC7A11 pathway
Authors: Tang Jie , Liu Wenqiang , Li Zihan , Shen Can , Zhang Longbiao , Wang Cheng , Wang Fengshuo , Zai Zhuoyan , Qian Xuewen , Hu Weirong , Zhang Xiaoyue , Peng Xiaoqing , Xu Yayun , Chen Feihu
Published: January 2025

The activation of acid‐sensing ion channel 1a (ASIC1a) in response to extracellular acidification leads to an increase in extracellular calcium influx, thereby exacerbating the degeneration of articular chondrocytes in rheumatoid arthritis (RA). It has been suggested that the inhibition of extracellular calcium influx could potentially impede chondrocyte ferroptosis. The cystine transporter, solute carrier family 7 member 11 (SLC7A11), is recognized as a key regulator of ferroptosis. Recent studies suggest that the tumor suppressor gene p53 facilitates the induction of ferroptosis by suppressing the upregulation of SLC7A11. This process is mediated by the nuclear factor erythroid 2‐related factor 2 (NRF2), a key transcription factor integral to the maintenance of cellular redox homeostasis and the regulation of inflammatory responses. This study aims to investigate the role of ASIC1a in the ferroptosis of RA chondrocytes and to determine the involvement of the p53/NRF2/SLC7A11 pathway in its underlying mechanism. In vitro experiments revealed that acidosis induces ferroptosis and reduces the expression of NRF2 and SLC7A11 in chondrocytes. Moreover, acidification significantly increased p53 protein levels in chondrocytes. Pifithrin‐α (PFN‐α), a p53 inhibitor, mitigated acidosis‐induced ferroptosis and restored the diminished expression of NRF2 and SLC7A11. Furthermore, PcTx‐1, an ASIC1a inhibitor, inhibited acidification‐induced ferroptosis, enhanced the protein levels of SLC7A11 and NRF2, and reduced p53 expression. In vivo experiments demonstrated that the ASIC1a‐specific inhibitor PcTx‐1 ameliorated histopathological characteristics of ankle joints in collagen‐induced arthritis (CIA) mice, decreased p53 expression, and enhanced NRF2 and SLC7A11 expression in chondrocytes. These findings suggest that ASIC1a inhibition may mitigate acidification‐induced ferroptosis in articular chondrocytes in RA, potentially via the p53/NRF2/SLC7A11 pathway.
A Core Outcome Set for Adult General ICU Patients
Authors: Kjær Maj-Brit Nørregaard , Bruun Camilla Rahbek Lysholm , Granholm Anders , Møller Morten Hylander , Rasmussen Bodil Steen , Mortensen Camilla Bekker , Poulsen Lone Museaus , Strøm Thomas , Laerkner Eva , Brøchner Anne Craveiro , Haberlandt Trine , Bunzel Anne-Marie Gellert , Herløv Louise Stenbryggen , Holm Anna , Sivapalan Praleene , Estrup Stine , Cronhjort Maria , Schandl Anna , Laake Jon Henrik , Hofsø Kristin , Blokzijl Fredrike , Keus Frederik , Pfortmueller Carmen Andrea , Ostermann Marlies , Cole Jade M. , Wise Matt P. , Szczeklik Wojciech , Wludarczyk Anna , Jovaiša Tomas , Cecconi Maurizio , Sigurdsson Martin Ingi , Nalos Marek , Hästbacka Johanna , Mäkinen Marja , Hammond Naomi , Litton Edward , Haines Kimberley , Myatra Sheila Nainan , Vijayaraghavan Bharath Kumar Tirupakuzhi , Yadav Kavita , Jha Vivekanand , Venkatesh Balasubramanian , Egerod Ingrid , Perner Anders , Collet Marie O.
Published: January 2025

Objectives:

Randomized clinical trials informing clinical practice (e.g., like large, pragmatic, and late-phase trials) should ideally mostly use harmonized outcomes that are important to patients, family members, clinicians, and researchers. Core outcome sets for specific subsets of ICU patients exist, for example, respiratory failure, delirium, and COVID-19, but not for ICU patients in general. Accordingly, we aimed to develop a core outcome set for adult general ICU patients.

Design:

We developed a core outcome set in Denmark following the Core Outcome Measures in Effectiveness Trials Handbook. We used a modified Delphi consensus process with multiple methods design, including literature review, survey, semi-structured interviews, and discussions with initially five Danish research panels. The core outcome set was internationally validated and revised based on feedback from research panels in all countries.

Setting:

There were five Danish research panels and 17 panels in 13 other countries. Interviews and the three-round Delphi survey was conducted in Denmark, followed by validation of the core outcome set across 14 countries in Europe, Australasia, and India.

Subjects:

Adult ICU survivors, family members, clinicians, and researchers.

Interventions:

None.

Measurements and Main Results:

We identified 329 published outcomes, of which 50 were included in the 264 participant Delphi survey. In semi-structured interviews of 82, no additional outcomes were added. The first Delphi survey round was completed by 249 (94%) participants, and 202 (82%) contributed to the third and final round. The initial core outcome set comprised six outcomes. International validation involved 217 research panel members and resulted in the final core outcome set comprising survival, free of life support, free of delirium, out of hospital, health-related quality of life, and cognitive function.

Conclusions:

We developed and internationally validated a core outcome set with six core outcomes to be used in research, specifically clinical trials involving adult general ICU patients.
Effect of Anterior Chamber Air Injection on Intraocular Lens Stability after Phacovitrectomy with Gas/Air Tamponade
Authors: Zhou Zigan , Sun Bi , Wu Xingyi , Liu Yuhao , Guo Binghua , Yang Chen , Lin Zhong , Wu Ronghan
Published: January 2025

Purpose:

Anterior chamber air injection (ACAI) is a surgical technique used to decrease the occurrence of postoperative intraocular lens (IOL) haptic dislocation following phacovitrectomy with gas/air tamponade. The impact of this technique on IOL stability remains uncertain, prompting the design of this study to investigate further.

Methods:

This study included 51 eyes of 51 patients who underwent phacovitrectomy with gas/air tamponade. The patients were divided into two groups: Group 1 (ACAI group, 26 eyes) and Group 2 (non-ACAI group, 25 eyes). IOL position (IOLP) is used to determine the IOL axial movement. The study analyzed changes in lens/IOL decentration, tilt, and aqueous depth (AQD) using repeated measures analysis of variance. The linear regression model was employed to investigate the factors influencing the IOL stability.

Results:

There was no significant difference in IOL decentration, tilt, mean prediction error, and mean absolute error between the two groups. ACAI not only caused the IOLP to move axially forward but also the AQD to take longer to stabilize. Preoperative lens tilt is a significant factor influencing postoperative IOL tilt. Additionally, sex, ACAI, and aqueous width are identified as factors that affect IOLP.

Conclusion:

ACAI is a factor that can affect IOL instability, and the surgeon needs to consider the necessity of ACAI when performing phacovitrectomy with gas/air tamponade.
EUS-Guided Gastroenterostomy for Benign Gastric Outlet Obstruction
Authors: Canakis Andrew , Tugarinov Nicol , Bapaye Jay , Gilman Andrew J. , Hathorn Kelly E. , Twery Benjamin , Sharaiha Reem Z. , Baron Todd H. , Irani Shayan S.
Published: January 2025

Background and Aims:

Gastric outlet obstruction (GOO) is a clinical manifestation of mechanical obstruction at the antropyloric region or proximal small bowel. The goal of endoscopic management is to relieve the obstruction so patients can resume per oral intake. Most studies have focused on malignant causes of GOO; yet only a handful have explored outcomes related to benign etiologies. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has emerged as a novel method to bypass the obstruction with a lumen apposing metal stent. In this systematic review and meta-analysis, we aim to explore the technical and clinical success of EUS-GE for benign GOO.

Methods:

Multiple databases were searched for studies looking at EUS-GE for benign GOO from inception until July 2024. The primary outcome was technical and clinical success. Secondary outcomes included rates of reintervention and adverse events (AE).

Results:

Ten studies met inclusion criteria (n=181 patients). The most common etiologies were from chronic (n=48) and acute (n=41) pancreatitis followed by peptic strictures (n=19) and surgical anastomotic strictures (n=13). The mean procedure time was 66 minutes. The pooled rate of technical success was 95% (95% CI: 87.34-98.16; I
2=0%). The pooled rate of clinical success was 90.6% (95% CI: 81.1-95.4; I
2=0%). Total adverse events and reintervention rates were 11% (95% CI: 6.06-22.33; I
2=38.7%) and 7% (95% CI: 2.23-20.95; I
2=35.9%), respectively.

Conclusion:

The results of this meta-analysis demonstrate the efficacy and relative safety profile of EUS-GE for benign GOO. Further studies are needed to determine the optimal patient selection related to clinical success based on the underlying etiology.
Equity and the operational considerations of the kidney transplant allocation system
Authors: Mohan Sumit , Yu Miko , Husain S. Ali
Published: January 2025

Purpose of review

Demonstrate the impact of allocation system design on access to the waitlist and transplantation for patients with end-stage kidney disease (ESKD).

Recent findings

Minoritized groups are more likely to be declined from transplant listing owing to psychosocial criteria. Lack of consistent definitions, screening tools with differential subgroup validity, and insufficient evidence-base contribute to concerns about reliance on psychosocial factors in transplant listing decisions.

Although kidney transplantation is the preferred treatment choice, a shrinking proportion of prevalent patients are waitlisted for this option in the United States, even among our youngest ESKD patients. Recent HRSA proposals to expand data collection to encompass the prewaitlisting process suggest a timely need to capture additional data on transplant referrals to improve access to transplantation. In 2021, KAS250 was implemented in response to concerns of geographic inequities in transplant rates. However, updates to this system have also resulted in a dramatic rise in organ offers, the number of offers needed to successfully place an organ and lowered utilization rates. Since KAS250, the use of alternative pathways to improve organ utilization rates, such as out-of-sequence placements has increased dramatically across the organ quality spectrum and risk exacerbating disparities in access to transplant. Additionally, the current absence of meaningful oversight risks undermining the perception of the transplant system as an objective process.

There is a need for a more robust evaluation of recent iterative changes in waitlist and organ allocation practices to ensure equity in access for our most vulnerable patients.
Anemia and Cerebrovascular disease: pathophysiological insights and clinical implications
Authors: Obeagu Emmanuel Ifeanyi , Obeagu Getrude Uzoma
Published: January 2025

Anemia and cerebrovascular disease (CVD) are interconnected conditions that significantly impact global health, often coexisting to worsen clinical outcomes. Anemia-induced hypoxia increases the production of reactive oxygen species (ROS) via mitochondrial dysfunction and xanthine oxidase activity, amplifying oxidative stress. ROS directly harm endothelial cells by disrupting tight junctions, increasing vascular permeability, and compromising the integrity of the blood-brain barrier (BBB). This review delves into the pathophysiology of anemia in the context of CVD, emphasizing the impact of hypoxia, oxidative stress, and endothelial dysfunction. Clinically, anemia worsens CVD prognosis by elevating the risk of ischemic and hemorrhagic strokes, delaying recovery, and increasing mortality rates. If untreated, anemia exacerbates neuronal damage, promotes vascular remodeling, and perpetuates systemic inflammation, leading to poor functional outcomes. This review underscores the necessity of timely anemia diagnosis and targeted management in patients with cerebrovascular disease to mitigate these adverse outcomes.
Development and Testing of an Objective Structured Clinical Examination for Evaluating Nurses in Infusion Therapy
Authors: Meszaros Mariana de Jesus , de Almeida Angélica Olivetto , Aoki Roberta Nazario , Vieira Ana Paula Gadanhoto , Castelani Mariana Aparecida , Silva Juliany Lino Gomes , Lima Maria Helena de Melo , Oliveira-Kumakura Ana Railka de Souza
Published: January 2025

This study aimed to develop, assess, and test an Objective Structured Clinical Examination (OSCE) to evaluate nurses’ competency in planning and managing infusion therapy. The study adopted a methodological approach with a quantitative design and was conducted from December 2020 to August 2021 at a university hospital in São Paulo, Brazil. Data collection occurred in 3 stages: development of scenarios and assessment checklists, evaluation of expert consensus, and testing scenarios with the target audience. Data analysis involved calculating the Modified Kappa coefficient. The OSCE comprised 8 clinical stations, designed based on the theoretical framework of the Vessel Health and Preservation model and the Infusion Therapy Standards of Practice, which delineate evidence-based procedures for vascular access and infusion therapy. During expert assessment and examination testing, all evaluated items demonstrated coefficient values ≥0.74. Thus, the study successfully developed evidence-based OSCE for infusion therapy, showing strong expert consensus. Testing with nurses yielded positive outcomes, affirming the effectiveness of the educational practice’s design and structure.
Evaluation of Generative Artificial Intelligence Models in Predicting Pediatric Emergency Severity Index Levels
Authors: Ho Brandon , Lu Meng , Wang Xuan , Butler Russell , Park Joshua , Ren Dennis
Published: January 2025

Objective

Evaluate the accuracy and reliability of various generative artificial intelligence (AI) models (ChatGPT-3.5, ChatGPT-4.0, T5, Llama-2, Mistral-Large, and Claude-3 Opus) in predicting Emergency Severity Index (ESI) levels for pediatric emergency department patients and assess the impact of medically oriented fine-tuning.

Methods

Seventy pediatric clinical vignettes from the ESI Handbook version 4 were used as the gold standard. Each AI model predicted the ESI level for each vignette. Performance metrics, including sensitivity, specificity, and F1 score, were calculated. Reliability was assessed by repeating the tests and measuring the interrater reliability using Fleiss kappa. Paired t tests were used to compare the models before and after fine-tuning.

Results

Claude-3 Opus achieved the highest performance amongst the untrained models with a sensitivity of 80.6% (95% confidence interval [CI]: 63.6–90.7), specificity of 91.3% (95% CI: 83.8–99), and an F1 score of 73.9% (95% CI: 58.9–90.7). After fine-tuning, the GPT-4.0 model showed statistically significant improvement with a sensitivity of 77.1% (95% CI: 60.1–86.5), specificity of 92.5% (95% CI: 89.5–97.4), and an F1 score of 74.6% (95% CI: 63.9–83.8, P < 0.04). Reliability analysis revealed high agreement for Claude-3 Opus (Fleiss κ: 0.85), followed by Mistral-Large (Fleiss κ: 0.79) and trained GPT-4.0 (Fleiss κ: 0.67). Training improved the reliability of GPT models (P < 0.001).

Conclusions

Generative AI models demonstrate promising accuracy in predicting pediatric ESI levels, with fine-tuning significantly enhancing their performance and reliability. These findings suggest that AI could serve as a valuable tool in pediatric triage.
Biodistribution and Dosimetry Evaluation of the Radiolabeled Somatostatin Receptor Antagonist 68Ga-DATA5m LM4 in Molecular Imaging of Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors Patients
Authors: Ballal Sanjana , Sheokand Parvind , Yadav Madhav P. , Roesch Frank , Viswanathan Rahul , Satapathy Swayamjeet , Tripathi Madhavi , Moon Euy Sung , Mishra Prashant , Rastogi Sameer , Agarwal Shipra , Bal Chandrasekhar
Published: January 2025

Purpose

This study aimed to assess the biodistribution and radiation dosimetry of 68Ga-DATA5m LM4 in patients with gastroenteropancreatic neuroendocrine tumors.

Patients and Methods

Eight patients (5 females and 3 males) with various gastroenteropancreatic neuroendocrine tumors were included in the study. Each patient underwent 3 whole-body PET scans at 10, 60, and 120 minutes after receiving an IV injection of approximately 162.5 MBq of 68Ga-DATA5m LM4. Organs considered for dosimetric analysis included the liver, heart, spleen, kidneys, adrenal glands, and lumbar vertebrae (L2 to L4). Dosimetric calculations were performed using the OLINDA/EXM 2.2 software.

Results

Physiological uptake of 68Ga-DATA5m LM4 was observed in the pituitary gland, spleen, liver, adrenal glands, and the urinary tract (kidneys and urinary bladder) for all patients. The kidneys received the highest absorbed doses at (4.77E-02 ± 1.49E-02 mSv/MBq). The mean effective dose was 2.61E-03 ± 5.99E-04 mSv/MBq.

Conclusions

68Ga-DATA5m LM4 injection is safe and is primarily excreted through urine, delivering the highest radiation dose to the kidneys.
Impact of the Good Samaritan Law on bystander intervention willingness and perceived legal risks in India
Authors: Kewalramani Divya , Choron Rachel L. , Whitley Daniel , Teichman Amanda , Raina Karuna , Singh Gautam , Piplani Charoo , Englert Zachary , Hanna Joseph , Peck Gregory L. , Barie Philip S. , Tewari Piyush , Narayan Mayur
Published: January 2025

BACKGROUND

Road traffic crashes (RTCs) are a global health burden, particularly in India, where response times for first responders can be prolonged. Prior to enactment of a Good Samaritan Law (GSL) in 2016, involved bystanders could face criminal and financial liability for assisting at an RTC site. This study evaluates the impact of GSL on bystander RTC attitudes, awareness, and experiences in India, comparing outcomes pre- and post-GSL implementation across metropolitan cities (MCs) and nonmetropolitan cities (NMCs). We hypothesized that GSL would lead to increased bystander willingness to assist the RTC victim.

METHODS

This retrospective, cross-sectional, observational study analyzed data from two national surveys conducted in 2013 (pre-GSL, n = 1,027) and 2018 (post-GSL, n = 3,667) across 7 and 11 Indian cities, respectively. Difference-in-difference analysis, propensity score matching, and regression models were used to assess changes in willingness to assist RTC victims, awareness of GSL, legal and financial fears, and awareness of GSL.

RESULTS

Post-GSL implementation saw an increase in willingness to assist RTC victims (Δ = +65.4%, p < 0.001) and substantial decreases in fear regarding legal (Δ = −81%, p < 0.001) and financial consequences (Δ = −75.8%, p < 0.001) of rendering assistance. GSL awareness was higher in NMCs (n = 2,215, 31.2%) compared with MCs (n = 838, 9.25%) among general citizens (p < 0.001). Males showed higher willingness to assist RTC victims (p < 0.01), whereas individuals with postgraduate education demonstrated increased awareness of GSL (p < 0.01).

CONCLUSION

The implementation of GSL in India has transformed bystander intervention in RTCs, increasing the reported likelihood of assistance and substantially reducing legal and financial concerns. This shift demonstrates GSL's potential to improve outcomes for RTC victims. However, disparities in awareness between MCs and NMCs, as well as sex- and education-based differences, highlight the need for targeted educational campaigns. Future initiatives should focus on improving application of the law and strengthening the entire trauma chain of survival.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Burn-induced mitochondrial dysfunction in hepatocytes: The role of methylation-controlled J protein silencing
Authors: Pratap Akshay , Monge Kenneth Meza , Qualman Andrea C. , Kovacs Elizabeth J. , Idrovo Juan-Pablo
Published: January 2025

BACKGROUND

Burn injuries trigger a systemic hyperinflammatory response, leading to multiple organ dysfunction, including significant hepatic damage. The liver plays a crucial role in regulating immune responses and metabolism after burn injuries, making it critical to develop strategies to mitigate hepatic impairment. This study investigates the role of methylation-controlled J protein (MCJ), an inner mitochondrial protein that represses complex I in burn-induced oxidative stress and mitochondrial dysfunction, using an in vitro Alpha Mouse Liver 12 cell model.

METHODS

Alpha Mouse Liver 12 cells were treated with serum from burn-injured mice (SBIM) to simulate burn injury in vitro. Methylation-controlled J protein was silenced using shRNA. Cell viability, apoptosis markers, reactive oxygen species levels, antioxidant response elements, electron transport chain components, and mitochondrial respiration were assessed using various techniques, including Cell Counting Kit-8 assay, Western blotting, MitoSOX Red staining, and Seahorse XF analysis.

RESULTS

Serum from burn-injured mice treatment (10%) for 8 hours reduced Alpha Mouse Liver 12 cell viability to 50% of control levels and increased MCJ expression fivefold. It also significantly upregulated apoptosis markers: cleaved caspase-3 (4-fold), Bax (3.8-fold), and cytosolic cytochrome c (3.5-fold). Methylation-controlled J protein silencing improved cell viability to 85% of control levels and reduced apoptosis markers by 75% to 78%. Serum from burn-injured mice increased reactive oxygen species levels by 3-fold, while MCJ silencing reduced this by 2.5-fold. Antioxidant proteins (NRF2, HO-1, NQO-1, GCLC, catalase) were suppressed by SBIM but upregulated 3.2- to 3.8-fold with MCJ silencing. Serum from burn-injured mice reduced electron transport chain components (NDUFS1, SDHB, MTCO2) by 45% to 65%, which MCJ silencing restored 2.5- to 3-fold. Mitochondrial respiration improved significantly with MCJ silencing: basal respiration (+26%), maximal respiration (+66%), adenosine triphosphate production (+25%), and spare respiratory capacity (+63%).

CONCLUSION

Methylation-controlled J protein plays a critical role in burn-induced hepatocyte damage. Its silencing alleviates SBIM-induced cytotoxicity, oxidative stress, and mitochondrial dysfunction. These findings highlight MCJ as a potential therapeutic target for preserving liver function in burn patients, warranting further in vivo studies to explore its clinical potential.