bluuebunny/crossref_metadata_2025 huggingface dataset:
Social, Racial, and Economic Disparities Affecting Outcomes of Hypertensive Adolescents
Authors: Singhapakdi Kanya , Haydel Amelia , Johnston Marla , Yang Shengping , Bradford Tamara , Moulton Dedrick , Kimball Thomas R.
Published: January 2025

Essential hypertension is one of the most common conditions managed in pediatric cardiology and can result in lasting deleterious effects on the cardiovascular system. Pediatric hypertension is so prevalent in the United States that it is often referred to as a public health challenge.

Social determinants of health (SDH) are the cultural, economic, educational, healthcare accessibility, and political influences in the environment in which an individual is born or lives, all of which can affect that individual's overall health. This study investigated the impact of social determinants such as rurality, food insecurity, transportation challenges, minority status, income, and race on cardiovascular outcomes in adolescent patients with essential hypertension.

This study utilizes multiple validated tools including those from the United States Census and the United States Department of Agriculture (USDA). Using these tools, the patients were scored on their social vulnerability based on home address. These scores were then compared with their echocardiographic data, focusing on measures of end‐organ damage known to occur in the setting of hypertension, including but not limited to indexed left ventricular (LV) mass. LV mass is an independent risk factor for future adverse cardiovascular events.

In this study, more social vulnerability and low income were associated with a greater indexed LV mass (r = 0.18, p = 0.008). African American race was associated with a higher left atrial (LA) volume (p = 0.03). These findings substantiate that adolescents with essential hypertension are not only impacted by biological factors but also a combination of intersecting social constructs. The results of this study provide both a deeper understanding of the challenges these patients face and the opportunity to develop real‐life interventions that can optimize clinical outcomes.
First‐in‐Man Study of a Novel Peripheral Plaque Atherectomy Device
Authors: Wang Hui , Pan Dikang , Cui Shijun , Tong Zhu , Gao Xixiang , Gu Yongquan , Guo Jianming , Guo Lianrui
Published: January 2025

This first‐in‐man (FIM) study evaluated the feasibility and safety of a new peripheral plaque atherectomy system in patients with symptomatic lower extremity artery disease (LEAD). Ten patients with symptomatic LEAD (Rutherford class 2–5) were enrolled in a prospective, single‐center study from March to April 2024. Patients aged 18–85 years with target lesions showing ≥70% stenosis and reference vessel diameters ≥1.8 mm underwent treatment using a novel atherectomy device with a “shaving” mechanism to excise calcified plaques. Outcomes included post‐procedural stenosis improvement, 6‐month primary patency rate, and safety endpoints such as thrombosis, vasospasm, acute occlusion, and distal embolization. Statistical analysis used SPSS 23.0. Ten male patients (mean age: 61.4 ± 9.2 years) were treated. Most had diabetes (80%), hypertension (70%), and hyperlipidemia (80%). Pre‐procedural ankle‐brachial index (ABI) averaged 0.50 ± 0.14. Angiographic analysis showed 60% of lesions in the femoral artery and 40% as chronic total occlusions. No major adverse events occurred, with 100% technical success. Post‐procedural ABI improved to 0.92 ± 0.12 (p < 0.05). At 6 months, the primary patency rate was 100%, with no clinically‐driven revascularization or adverse cardiovascular events. Mortality was 0%. All patients reported significant improvement in symptoms and walking distance, as well as enhanced quality of life and reduced pain during physical activity. The novel atherectomy device showed promising safety and efficacy for treating calcified LEAD. Larger‐scale trials are needed to confirm these outcomes.
Indole‐3‐Lactic Acid Inhibits Doxorubicin‐Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway
Authors: Lian Jiangfang , Lin Hui , Zhong Zuoquan , Song Yongfei , Shao Xian , Zhou Jiedong , Xu Lili , Sun Zhenzhu , Yang Yongyi , Chi Jufang , Wang Ping , Meng Liping
Published: January 2025

The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which is primarily attributed to its interaction with iron in mitochondria, leading to lipid peroxidation and myocardial ferroptosis. This study aimed to investigate the role of the gut microbiota‐derived metabolite, indole‐3‐lactic acid (ILA), in mitigating DOX‐induced cardiotoxicity (DIC). Cardiac function, pathological changes, and myocardial ferroptosis were assessed in vivo. The cardioprotective effects and mechanisms of ILA were explored using multi‐omics approaches, including single‐nucleus RNA sequencing (snRNA‐seq) and bulk RNA‐seq, and were further validated in Nrf2 knockout mice. The findings revealed that DOX treatment disrupted gut microbiota, significantly reducing the levels of the tryptophan metabolite ILA. In DIC models, ILA supplementation markedly improved cardiac function, reduced collagen deposition, and mitigated cardiac atrophy. The bulk and snRNA‐seq analyses indicated that myocardial ferroptosis played a crucial role in the cardioprotective effects of ILA. Experimental data demonstrated that ILA decreased DOX‐induced ferroptosis in both DIC mice and DOX‐treated H9C2 cells, evidenced by restoration of GPX4 and SLC7A11 levels and reduction of ACSL4. Mechanistically, ILA functions as a ligand for the aryl hydrocarbon receptor (AhR), leading to the upregulation of Nrf2 expression. The protective effects of ILA against ferroptosis were abolished by silencing AhR. Moreover, the beneficial effects of ILA on DIC were eliminated in Nrf2‐deficient mice. In conclusion, ILA exerts therapeutic effects against DIC by inhibiting ferroptosis through activation of the AhR/Nrf2 signalling pathway. Identifying the cardioprotective role of the microbial metabolite ILA could offer viable therapeutic strategies for DIC.
Integrated Analysis of Bulk RNA Sequencing, eQTL, GWAS, and Single‐Cell RNA Sequencing Reveals Key Genes in Hepatocellular Carcinoma
Authors: Gong Mingkai , Zhao Xian , Li Qingze , Hao Qisheng , Cha Lichao , Dong Guofei , Li Xinyu , Qiu Fabo , Li Dan , Tian Lantian
Published: January 2025

Hepatocellular carcinoma (HCC) poses a continual therapeutic challenge owing to its elevated incidence and unfavourable prognosis, underscoring the critical need for the discovery of new molecular targets for detection and therapy. This work included the analysis of three publically accessible HCC datasets from TCGA and GEO. Instrumental variables (IVs) were derived via expression quantitative trait loci (eQTL) analysis, then followed by two‐sample Mendelian randomisation (MR) analysis utilising publically available summary statistics. Key disease‐associated genes were identified by assessing odds ratios and connecting them with differentially expressed genes across the datasets. The potential molecular mechanisms of these genes were clarified by functional enrichment analysis, clinical data analysis, single‐cell RNA sequencing, GSEA, immune cell infiltration, and immune checkpoint analysis. These findings were then confirmed by Western blotting, immunohistochemistry, and quantitative PCR. By synthesising the outcomes from differential analysis of the databases, we found two genes, SERPING1 and STEAP3, that may be crucial in the beginning and development of HCC. These genes have a role in vital biological pathways and functions, such as metabolic regulation and macrophage activation. The significance of immunological‐mediated processes in HCC was further highlighted by CIBERSORT analysis, which revealed a specific pattern of immune cell infiltration and the location of immunological checkpoints in the illness. The findings elucidate the molecular mechanisms of HCC and underscore critical genes implicated in its pathogenesis. SERPING1 and STEAP3 affect tumour cells and modify the tumour microenvironment (TME), indicating that targeting these genes may offer a viable immunotherapeutic approach for HCC in clinical settings.
Metrnl and Cardiomyopathies: From Molecular Mechanisms to Therapeutic Insights
Authors: Xu Miaomiao , Liu Xiaoguang , Lu Liming , Li Zhaowei
Published: January 2025

Cardiomyopathies, a diverse group of diseases affecting the heart muscle, continue to pose significant clinical challenges due to their complex aetiologies and limited treatment options targeting underlying genetic and molecular dysregulations. Emerging evidence indicates that Metrnl, a myokine, adipokine and cardiokine, plays a significant role in the pathogenesis of various cardiomyopathies. Therefore, the objective of this review is to examine the role and mechanism of Metrnl in various cardiomyopathies, with the expectation of providing new insights for the treatment of these diseases.
A Twist on Injection Molding: Injecting Conventional Resin Composites
Authors: Vargas Marcos A. , Margeas Robert
Published: January 2025

Purpose

This article presents a different approach to injectable techniques. This technique uses conventional viscosity materials to achieve maximum strength and esthetics.

Clinical Considerations

The use of high‐viscosity material which has the strongest physical properties is desirable since failure of anterior resin composite has been described as fracture and recurrent decay. By incorporating changes to the conventional injection technique, heating and making bigger access wholes on the matrix allows the utilization of higher conventional viscosity materials.

Conclusions

The use of higher viscosity materials while using injectable techniques is possible by heating and providing a bigger access entrance to composite resin compules.
Reimagining André Rey's method for recording the copy process of the Rey Complex Figure Test: A commentary
Authors: Kuruvilla Maneesh V. , Blazely Angela
Published: January 2025

In 1941, André Rey published the Rey Complex Figure, a widely used test for assessing visual‐constructional ability and visual memory. It consists of two parts: copy and recall. Evaluating the copy portion presents challenges, as it requires the administrator to focus on both the process and outcome. The assessor must systematically track how the patient copies the figure in real‐time to evaluate their planning, organisation and executive abilities. This ‘clinician's copy’ serves as a record of the patient's approach, aiding later judgements about their cognitive skills. To ensure accuracy, clinicians need a method to record this process for later review or colleague consultation. This paper revisits Rey's suggestion of using different coloured pencils to observe the copy sequence, proposing an alternative. Instead of providing coloured pencils to the patient, we recommend that the administrator use them to record the copy sequence. This method aligns with test norms, reducing potential distractions for the patient while enabling both experienced and novice administrators to easily track and document the sequence of copying.
Oil Shocks and the Financial Markets: A Review
Authors: Ma Feng , Lu Xinjie , Vigne Samuel A.
Published: January 2025

Leading to enormous effects on the global financial markets, oil shocks have received full attention from academic literature. The objective of this survey is to organize and consolidate existing theoretical and empirical research on oil shocks and financial markets, with the goal of uncovering potential areas for future investigation. The paper begins with a brief overview of oil shocks against a historical background, and makes a summarized survey of the existing literature regarding oil shocks. Then this paper discusses the underlying sources of the oil shocks and then turns to make a review of the connections between oil shocks and the economy, the stock market, and the commodity market. The paper concludes with recommendations for subsequent research endeavors, and hopes to facilitate further research in the many strands of the oil shocks‐related literature.
Bridging the Principle‐Implementation Gap: Evaluating organizational change to achieve interoperability between the UK Emergency Services
Authors: Power Nicola , Philpot Richard , Levine Mark , Alcock Jennifer
Published: January 2025

Improving inter‐agency working across organizations is an important goal across public and private sectors. The UK Emergency Services have spent a decade implementing organizational change to improve interoperability between the Police, Fire and Ambulance Services. JESIP—the group tasked with realising this change—have faced criticism. We evaluated JESIP's efforts by interviewing expert commanders, finding participants supported the principle of change, but issues impeded its implementation. We developed the Principle‐Implementation Change Framework for Interoperability (PICI) to describe the gap between change principles and change implementation, identifying the macro‐systemic, meso‐organizational and micro‐psychological processes between them. Key obstacles to implementation included macro‐level funding issues, incompatible meso‐level organizational structures and strained micro‐level peer‐to‐peer relationships. Participants also reflected on the facilitators of change. At the meso‐organizational level, JESIP was perceived to have improved inter‐team communication and flexibility. At the micro‐psychological level participants described enhanced trust, shared identities and the emergence of a new type of interoperability leader. This study highlights the importance of gaining support for the principle of interoperability while addressing implementation challenges posed by the inherent social complexities involved in this change. Change efforts must be monitored over time, considering the macro, meso and micro‐level processes that influence the principle‐implementation gap.
Factoring fu Variability Into Estimates of Unbound Drug Concentrations Negatively Biases the MIC Versus % Probability of Target Attainment Relationship of Antimicrobial Agents
Authors: Martinez Marilyn N. , Papich Mark G. , Toutain Pierre‐Louis
Published: January 2025

The clinical breakpoint for a drug–pathogen combination reflects the drug susceptibility of the pathogen wild‐type population, the location of the infection, the integrity of the host immune response, and the drug–pathogen pharmacokinetic (PK)/pharmacodynamic (PD) relationship. That PK/PD relationship, along with the population variability in drug exposure, is used to determine the probability of target attainment (PTA) of the PK/PD index at a specified minimum inhibitory concentration (MIC) for a selected target value. The PTA is used to identify the pharmacodynamic cutoff value (COPD), which is one of the three components used to establish the clinical breakpoint. A challenge encountered when defining the COPD is that the available PK information typically reflects total (free plus protein‐bound) plasma concentrations. However, it is the unbound drug concentrations that exert the therapeutic effects and how the population fraction unbound (fu) incorporated into the COPD assessments can markedly influence the COPD. Factors examined included the estimated population fu mean (risk of bias) and the incorporation of estimated fu population variability into the Monte Carlo simulations when converting total to unbound plasma concentrations (risk of inflating variability). In this in silico study, the drug fu, systemic clearance, and the variability of both were altered so that the relative impact of each could be explored. We demonstrate that incorporating fu variability into the estimation of fAUCback can bias the COPD assessment and that the magnitude of bias reflects the relative variability in systemic clearance and fu.
Dose–response analysis of music intervention for improving delirium in intensive care unit patients: A systematic review and meta‐analysis
Authors: Dai Rong‐Sian , Wang Tsuei‐Hung , Chien Shao‐Yun , Tzeng Ya‐Ling
Published: January 2025

Background

Delirium is a common and severe condition among adult intensive care unit (ICU) patients. Music intervention, as a non‐pharmacological approach, has the potential to reduce delirium, but the optimal dosage and type of intervention remain unclear.

Aim

To explore the effects of music intervention at different doses and types on reducing delirium in ICU patients.

Study Design

This study was conducted as a systematic review and meta‐analysis. Databases including Cochrane Library, EBSCO, Embase, PubMed, Web of Science, Airiti Library, China National Knowledge Infrastructure and Wanfang Data were searched until 29 February 2024. Study quality was assessed using the Cochrane Risk of Bias 2.0 criteria. Data were analysed using RevMan 5.4.1 and Comprehensive Meta‐Analysis 3.0.

Results

Fourteen studies involving 1434 ICU patients were included. Four studies were of good quality (low risk of bias), seven were of moderate quality (unclear risk) and three were of low quality (high risk). Pooled analysis showed that music interventions significantly reduced the risk of delirium (12 studies, RR = .49, 95% confidence interval [CI] [.40, .61]). Slow‐tempo music had the strongest effect (11 studies, RR = .46, 95% CI [.37, .57]). The optimal intervention dosage involves conducting music interventions twice daily (12 studies, RR = .46, 95% CI [.34, .63]), with each session lasting 30 min (12 studies, RR = .41, 95% CI [.30, .55]). Additionally, a pooled analysis showed that a 7‐day music intervention (6 studies, RR = .43, 95% CI [.26, .71]) was the most effective in reducing the risk of delirium.

Conclusions

Music intervention reduces delirium in ICU patients, especially with two 30‐min sessions daily for 7 days. However, the certainty of evidence is low, highlighting the need for further high‐quality research.

Relevance to Clinical Practice

Music intervention is a simple, non‐invasive method that may help reduce delirium in ICU patients. However, given the low certainty of the current evidence, it should be used cautiously, and further research is needed to validate its effectiveness before routine implementation.
Unveiling the conceptual and intellectual map of care bundle research in ICUs: Trends, key issues, and collaborative networks
Authors: Özkan İlknur , Dünya Cansu Polat , Taylan Seçil
Published: January 2025

Background

Care bundles are evidence‐based practices intended to improve patient outcomes and have become a significant focus in intensive care.

Aim

This study aims to identify research trends, key topics, leading researchers, and significant collaborations in care bundle research within ıntensive care units by mapping the conceptual and intellectual structure of the field.

Study Design

Data were collected from the Web of Science database, covering publications from 2010 to 2024. The search terms included ‘bundle*’ or ‘bundle* care’ and ‘intensive care unit’ or ‘critical care’. The analysis used tools like the Biblometrix package in R and VOSviewer, focusing on performance metrics, co‐citation analysis, co‐occurrence network analysis, and thematic mapping.

Results

The annual growth rate of publications on care bundles is 6.26%. The most prolific journals include Critical Care Medicine, the American Journal of Infection Control, and Infection Control and Hospital Epidemiology. Thematic mapping shows research is concentrated on critical areas such as infection control, patient safety, and quality improvement. While some themes, like ‘intensive care units’ and ‘central line‐associated bloodstream infection’, are well‐developed and central, others like ‘maternal safety consensus’ and ‘safety consensus bundle’ are highly developed but less central. Emerging themes like ‘acute kidney injury’ suggest potential areas for future research.

Conclusions

This bibliometric analysis offers a comprehensive overview of intensive care unit care bundle research, highlighting a strong focus on critical issues like infection control, patient safety, and care quality improvement.

Relevance to Clinical Practice

The study provides crucial insights for clinical practice by identifying key research trends and underexplored topics related to intensive care unit care bundles. These findings can guide the development of more effective care protocols, promote multidisciplinary collaboration, and enhance healthcare professional education, ultimately contributing to optimized patient care and high standards in the intensive care unit through improved care bundle implementation.
Task Difficulty and Gender Differences in Competitiveness: Evidence From Botswana
Authors: Drouvelis Michalis , Pearce Graeme
Published: January 2025

Using a novel subject pool from Botswana, we experimentally examine the impact of task difficulty on willingness to compete, an economic indicator that may partially explain gender disparities in the labour market. Our experiment closely follows the paradigm of Niederle and Vesterlund (2007, QJE) and is concerned with treatments where a task is either relatively easy or more difficult. We report evidence of a larger gender gap in willingness to compete when the math task is easy in comparison to when the math task is more difficult. Our results have implications for future experiments examining gender differences.
Teacher Bias and Evaluation Differences in Test Scores: Different Methods for Different Questions
Authors: Delaney Judith M. , Devereux Paul J.
Published: January 2025

We study differences in teacher evaluations of student performance relative to those measured by test scores. While much literature is concerned with estimating various types of teacher biases, we show conceptually that there is no single ‘teacher bias’ effect. Even if teachers have no group bias, teacher evaluation differences by group masystematically deviate from test score differences if the distribution of test scores differs across groups. Commonly used approaches are not equivalent and can lead to different conclusions as they target different estimands. We demonstrate our findings using Monte Carlo simulations and, using two recent UK cohort surveys, we show that these conceptual issues matter in practice when we evaluate whether teachers are likely to over‐estimate female performance in English. Finally, we use the methods to examine an issue of substantive importance, gender differences in teacher perceptions in comparative advantage in English relative to mathematics. Our findings suggest that it is unlikely that teacher misperceptions of comparative advantage by gender are an important cause of the gender gap in STEM.
Social Technologies in the Perception of Rural Extensionists in Brazil
Authors: Ribeiro Marques Viviane , Lone Todd , Barbe Luciane , Pereira Anderson , Azevedo Mota Diego , Redin Ezequiel , Xu Pei , Siqueira Jeanne , Vasconcelos Melo Thiago
Published: January 2025

Social Technologies are technologies that are adapted to make self-managed enterprises economically viable through a set of transformative techniques and methodologies that promote social inclusion and improve quality of life. This study analyzed rural extension workers' perception of social technologies in technical assistance and rural extension (TARE) services in Brazil. This quantitative study used an online questionnaire, directed at TARE professionals in Brazil, with 575 respondents on the perception of rural extension workers. Analysis of variance was performed using the F-test to compare the means of each set of questions. The proportions of responses were compared using the chi-square test and Fisher's test at a probability level of 5%. Based on the perceptions of the rural extension workers, it was confirmed that most rural extension workers understand the importance of social technologies, and the majority, regardless of region, have similar thinking about social technologies. According to the specificities of each region in Brazil, work can be done to focus on the deficiencies of each extensionist concerning knowledge and work with social technologies. The deficiencies of each extensionist with knowledge and work with social technologies are associated with regional characteristics and the specific demands of each region.
Sparse deconvolution beamforming with non-negative L1−αL2 regularization for acoustic source localization
Authors: Du Zhaohui , Zhu Yinan , Zhang Han , Wang Xuchen , Lu Wenyan
Published: January 2025

This letter proposed a sparse deconvolution localization method (FFT-L1ML2) driven by non-convex L1−αL2 regularization that more closely approximates the ideal L0 norm. It is an alternative that explores the sparse structure of sound sources to enhance localization accuracy, while the original sparse deconvolution beamforming lacks a sufficiently accurate sparse description. An optimization solver composed of forward gradient descent and backward proximal operator is then developed for the FFT-L1ML2 model to reconstruct the beamforming map. Both simulation and experimental results show the effectiveness and superiority of the proposed method in localization accuracy, energy concentration, pseudo source reduction, and computational cost.
A Characterization of Physical Activity in People Living With Advanced Multiple Sclerosis
Authors: Ludgate Julia , Edwards Thomas , Cardwell Katherine , Fakolade Afolasade , Pilutti Lara A.
Published: January 2025

Little is known about physical activity (PA) participation in people with advanced multiple sclerosis (MS). The purpose of this study was to (a) characterize self-reported PA levels and (b) explore how PA levels might differ based on sociodemographic (e.g., gender) and clinical (e.g., MS clinical course) characteristics in people with advanced MS. We used a cross-sectional online survey design with 101 participants. PA was measured using the Physical Activity Scale for Individuals With Physical Disabilities. The mean score on the scale was 4.5 (SD = 5.9) metabolic equivalent hours per day. There was a significant difference in scores based on employment, population density, living situation, disability, and assistive-device type (all p < .05). PA levels were higher in those who were employed, lived alone, required bilateral support for mobility, and were manual wheelchair users (all p < .05). This study highlights low PA levels in people with advanced MS and potential variables that might impact PA in this MS subgroup.
ZDHHC2 promoted antimycobacterial responses by selective autophagic degradation of B-RAF and C-RAF in macrophages
Authors: Sheng Junli , You Xiaolong , Nie Dingnai , Fu Yuling , Ling Qiao , Yang Xiaodan , Chen Yitian , Ma Li , Hu Shengfeng
Published: January 2025

S-Palmitoylation is a reversible post-translational modification involving saturated fatty acid palmitate-to-cysteine linkage in the protein, which guides many aspects of macrophage physiology in health and disease. However, the precise role and underlying mechanisms of palmitoylation in
Mycobacterium tuberculosis
infection of macrophages remain elusive. Here, we found that
M. tuberculosis
infection induced the expression of zinc-finger DHHC domain–type palmitoyl-transferases (ZDHHCs), particularly ZDHHC2, in mouse macrophages. Furthermore, ZDHHC2 deficiency in mouse macrophages impaired the immunity against
M. tuberculosis
and reduced the production of various proinflammatory cytokines. Mechanistic studies revealed the involvement of ZDHHC2 in mediating the palmitoylation of B-RAF and C-RAF, affecting their autophagic degradation and stabilizing protein levels. The increased abundance of B-RAF and C-RAF subsequently increases the activity of the extracellular signal–regulated kinase (ERK) signaling pathway, affecting the survival of
M. tuberculosis
within macrophages. These findings suggest that ZDHHC2 is a potential target for treating tuberculosis.
Massively parallel barcode sequencing revealed the interchangeability of capsule transporters in
Streptococcus pneumoniae
Authors: Chua Wan-Zhen , Wong Rachel Lyn Ee , Chun Ye-Yu , Shien Nicole Ng Chyi , Su Tong , Maiwald Matthias , Chew Kean Lee , Lin Raymond Tzer-Pin , Hockenberry Alyson M. , Luo Min , Sham Lok-To
Published: January 2025

Multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) family transporters are essential in glycan synthesis, flipping lipid-linked precursors across cell membranes. Yet, how they select their substrates remains enigmatic. Here, we investigate the substrate specificity of the MOP transporters in the capsular polysaccharide (CPS) synthesis pathway in
Streptococcus pneumoniae
. These capsule flippases collectively transport more than 100 types of capsule precursors. To determine whether they can substitute for one another, we developed a high-throughput approach to systematically examine nearly 6000 combinations of flippases and substrates. CPS flippases fall into three groups: relaxed, type-specific, and strictly specific. Cargo size and CPS acetylation affect transport, and we isolated additional gain-of-function flippase variants that can substitute for the peptidoglycan flippase YtgP (MurJ). We also showed that combining flippase variants in a single cassette allows various CPS precursors to be flipped, which may aid glycoengineering. This study reveals that MOP flippases exhibit broad specificity, shaping the evolution of glycan synthesis.
The oxygen level in air directs airway epithelial cell differentiation by controlling mitochondrial citrate export
Authors: Kim Bo Ram , Rauckhorst Adam J. , Chimenti Michael S. , Rehman Tayyab , Keen Henry L. , Karp Philip H. , Taylor Eric B. , Welsh Michael J.
Published: January 2025

Oxygen controls most metazoan metabolism, yet in mammals, tissue O
2
levels vary widely. While extensive research has explored cellular responses to hypoxia, understanding how cells respond to physiologically high O
2
levels remains uncertain. To address this problem, we investigated respiratory epithelia as their contact with air exposes them to some of the highest O
2
levels in the body. We asked how the O
2
level in air controls differentiation of airway basal stem cells into the ciliated epithelial cells essential for clearing airborne pathogens from the lung. Through a metabolomics screen and
13
C tracing on primary cultures of human airway basal cells, we found that the O
2
level in air directs ciliated cell differentiation by increasing mitochondrial citrate export. Unexpectedly, disrupting mitochondrial citrate export elicited hypoxia transcriptional responses independently of HIF1α stabilization and at O
2
levels that would be hyperoxic for most tissues. These findings identify mitochondrial citrate export as a cellular mechanism for responding to physiologically high O
2
levels.
SPT5 regulates RNA polymerase II stability via Cullin 3–ARMC5 recognition
Authors: Aoi Yuki , Iravani Leila , Mroczek Isabella C. , Gold Sarah , Howard Benjamin C. , Shilatifard Ali
Published: January 2025

The stability of RNA polymerase II (Pol II) is tightly regulated during transcriptional elongation for proper control of gene expression. Our recent studies revealed that promoter-proximal Pol II is destabilized via the ubiquitin E3 ligase cullin 3 (CUL3) upon loss of transcription elongation factor SPT5. Here, we investigate how CUL3 recognizes chromatin-bound Pol II as a substrate. Using an unbiased proteomic screening approach, we identify armadillo repeat-containing 5 (ARMC5) as a CUL3 adaptor required for VCP/p97-dependent degradation of SPT5-depleted, chromatin-bound Pol II. Genome-wide analyses indicate that ARMC5 targets promoter-proximal Pol II in a BTB domain–dependent manner. Further biochemical analysis demonstrates that interaction between ARMC5 and Pol II requires the transcriptional cyclin-dependent kinase 9 (CDK9), supporting a phospho-dependent degradation model. We propose that defective, promoter-proximal Pol II that lacks SPT5 is rapidly eliminated from chromatin in a noncanonical early termination pathway that requires CDK9-dependent interaction with the CUL3-ARMC5 ubiquitin ligase complex.
A cytochrome
bd
repressed by a MarR family regulator confers resistance to metals, nitric oxide, sulfide, and cyanide in
Chromobacterium violaceum
Authors: Batista Bianca B. , de Lima Vinicius M. , Will W. Ryan , Fang Ferric C. , da Silva Neto José F.
Published: January 2025

Chromobacterium violaceum
is a ubiquitous environmental pathogen. Despite its remarkable adaptability, little is known about the mechanisms of stress resistance in this bacterium. Here, in a screen for iron-susceptible transposon mutants, we identified a cytochrome
bd
that protects
C. violaceum
against multiple stresses. The two subunits of this cytochrome
bd
(CioAB) are encoded by the
cioRAB
operon, which also encodes a GbsR-type MarR family transcription factor (CioR). A ∆
cioAB
mutant strain was sensitive to iron and the iron-requiring antibiotic streptonigrin and showed a decrease in siderophore production. Growth curves and survival assays revealed that the ∆
cioAB
strain was also sensitive to zinc, hydrogen peroxide, nitric oxide, sulfide, and cyanide. Expression analysis showed that the promoter activity of the
cioRAB
operon and the transcript levels of the
cioAB
genes were increased in a ∆
cioR
mutant. CioR bound the promoter region of the
cio
operon
in vitro
, indicating that CioR is a direct repressor of its own operon. Expression of the
cio
operon increased at high cell density and was dependent on the quorum-sensing regulator CviR. As cyanide is also a signal for
cio
expression, and production of endogenous cyanide is known to be a quorum sensing-regulated trait in
C. violaceum
, we suggest that CioAB is a cyanide-insensitive terminal oxidase that allows respiration under cyanogenic growth conditions. Our findings indicate that the cytochrome
bd
CioAB protects
C. violaceum
against multiple stress agents that are potentially produced endogenously or during interactions with a host.

IMPORTANCE

The terminal oxidases of bacterial respiratory chains rely on heme-copper (heme-copper oxidases) or heme (cytochrome
bd
) to catalyze the reduction of molecular oxygen to water.
Chromobacterium violaceum
is a facultative anaerobic bacterium that uses oxygen and other electron acceptors for respiration under conditions of varying oxygen availability. The
C. violaceum
genome encodes multiple respiratory terminal oxidases, but their role and regulation remain unexplored. Here, we demonstrate that CioAB, the single cytochrome
bd
from
C. violaceum
, protects this bacterium against multiple stressors that are inhibitors of heme-copper oxidases, including nitric oxide, sulfide, and cyanide. CioAB also confers
C. violaceum
resistance to iron, zinc, and hydrogen peroxide. This cytochrome
bd
is encoded by the
cioRAB
operon, which is under direct repression by the MarR-type regulator CioR. In addition, the
cioRAB
operon responds to quorum sensing and to cyanide, suggesting a protective mechanism of increasing CioAB in the setting of high endogenous cyanide production.
Insect-specific Alphamesonivirus-1 (
Mesoniviridae
) in lymph node and lung tissues from two horses with acute respiratory syndrome
Authors: Jurisic Lucija , Auerswald Heidi , Marcacci Maurilia , Di Giallonardo Francesca , Coetzee Laureen M. , Curini Valentina , Averaimo Daniela , Ortiz-Baez Ayda Susana , Cammà Cesare , Di Teodoro Giovanni , Richt Juergen A. , Holmes Edward C. , Lorusso Alessio
Published: January 2025

Members of the RNA virus order
Nidovirales
infect hosts ranging from marine invertebrates to terrestrial mammals. As such, understanding the determinants of host range in this group of viruses, as well as their patterns of emergence and disease potential, is of clear importance. The
Mesoniviridae
are a recently documented family within the
Nidovirales
. To date, mesoniviruses have only been associated with the infection of arthropod species, particularly mosquitoes, and hence are regarded as insect-specific viruses (ISVs). Herein, we report the first detection of a mesonivirus—Alphamesonivirus-1 —in mammals. Specifically, we utilized genomic and histological techniques to identify Alphamesonivirus-1 in lung and lymph node tissues of two horses (a mare and its foal) from Italy that succumbed to an acute respiratory syndrome. The genome sequences of Alphamesonivirus-1 obtained from the two horses were closely related to each other and to those from a local
Culex
mosquito pool and an Alphamesonivirus-1 previously identified in Italy, indicative of ongoing local transmission. The discovery of Alphamesonivirus-1 in horse tissues prompts further investigation into the host range of mesoniviruses, the possible role of insect-specific viruses in mammalian disease processes, the determinants of and barriers to cross-species virus transmission, and the potential epizootic threats posed by understudied viral families.

IMPORTANCE

Alphamesoniviruses, members of the family
Mesoniviridaeare,
are considered insect-specific RNA viruses with no known association with vertebrate hosts. Herein, we report the identification of Alphamesonivirus-1 in mammals. Using detailed molecular and histological analyses, we identified Alphamesonivirus-1 in lung and lymph node tissues of two horses that presented with an acute respiratory syndrome and that was phylogenetically related to virus sequences found in local
Culex
mosquitoes. Hence, Alphamesoniviruses may possess a broader host range than previously believed, prompting the investigation of their possible role in mammalian disease. This work highlights the need for increased surveillance of atypical viruses in association with unexplained respiratory illness, including those commonly assumed to be insect-specific, and may have implications for epizootic disease emergence.
Supplemental Material: Mechanisms of bedding fracturing in the Junggar Basin, northwest China: Constraints from in situ U-Pb dating and C-O-Nd isotopic analysis of calcite cements
Authors: Zhang Chen , al. et
Published: January 2025

Figure S1 and Tables S1–S4.
Validation of a Quadrupole Model of Sound Radiation of a Turbulent Jet Based on Multi-Microphone Acoustic Measurements
Authors: Kopiev V. F. , Chernyshev S. A. , Faranosov G. A. , Korobov A. A.
Published: January 2025

A low-order model of quadrupole sound sources in a turbulent jet has been developed using the acoustic analogy method. Multimicrophone acoustic measurements of jet sound radiation are used to estimate the model parameters and validate it. Based on measurements carried out in different zones of the sound field, estimates of the size of the effective localization region of sound sources are made and the boundaries of the zone of dominance of quadrupole sound radiation over pseudo-sound fluctuations are determined. The proposed model can be used in practical estimates of the spectral and correlation characteristics of the far and near sound field of the jet.
Puberty blockers for gender dysphoria in youth: A systematic review and meta-analysis
Authors: Miroshnychenko Anna , Roldan Yetiani , Ibrahim Sara , Kulatunga-Moruzi Chan , Montante Steven , Couban Rachel , Guyatt Gordon , Brignardello-Petersen Romina
Published: January 2025

Aim

Gender dysphoria (GD) refers to the psychological distress associated with the incongruence between one’s sex and one’s gender identity. To manage GD, individuals may delay the development of primary and secondary sex characteristics with the use of puberty blockers. In this systematic review, we assess and summarise the certainty of the evidence about the effects of puberty blockers in individuals experiencing GD.

Methods

We searched Medline, Embase, PsychINFO, Social Sciences Abstracts, LGBTQ+ Source and Sociological Abstracts from inception to September 2023. We included observational studies comparing puberty blockers with no puberty blockers in individuals aged <26 years experiencing GD, as well as before–after and case series studies. Outcomes of interest included psychological and physical outcomes. Pairs of reviewers independently screened articles, abstracted data and assessed risk of bias. We performed a meta-analysis and assessed the certainty of a non-zero effect using the grading of recommendations assessment, development and evaluation (GRADE) approach.

Results

We included 10 studies. Comparative observational studies (n=3), comparing puberty blockers versus no puberty blockers, provided very low certainty of evidence on the outcomes of global function and depression. Before–after studies (n=7) provided very low certainty of evidence addressing gender dysphoria, global function, depression, and bone mineral density.

Conclusions

There remains considerable uncertainty regarding the effects of puberty blockers in individuals experiencing GD. Methodologically rigorous prospective studies are needed to understand the effects of this intervention.

Trial registration number

PROSPERO CRD42023452171.
Epidemiology of gender dysphoria and gender incongruence in children and young people attending primary care practices in England: retrospective cohort study
Authors: Jarvis Stuart William , Fraser Lorna K , Langton Trilby , Hewitt Catherine Elizabeth , Doran Tim
Published: January 2025

Objective

To examine trends in diagnosis of gender dysphoria and related conditions in children and young people attending primary care practices in England.

Design

Longitudinal analysis of electronic primary care records from the Clinical Practice Research Datalink (CPRD) Aurum database linked to hospital and Index of Multiple Deprivation data.

Setting

Primary care practices in England between 2011 and 2021.

Participants

3782 patients aged 0–18 years with a recorded history of gender dysphoria/incongruence and matched comparators with autism spectrum conditions or eating disorder.

Main outcome measures

Incidence rates and prevalence of gender dysphoria/incongruence; prescribing rates for medical treatments; co-occurrence of anxiety, depression and self-harm.

Results

Between 2011 and 2021, incidence rates of recorded gender dysphoria/incongruence increased from 0.14 (95% CI 0.08 to 0.20) to 4.4 (95% CI 4.1 to 4.7) per 10 000 person years, and from 2014 the rate increased more rapidly in recorded females than males. There was no significant association between gender dysphoria/incongruence and area level deprivation. Of the 3782 children and young people with a record of gender dysphoria/incongruence, 176 (4.7%) were prescribed puberty suppressing hormones; 302 (8.0%) were prescribed masculinising/feminising hormones; and 1994 (52.7%) had a record of anxiety, depression or self-harm. Compared with matched comparators, those experiencing gender dysphoria/incongruence had similar recorded rates of anxiety and higher rates of depression and self-harm.

Conclusions

Recorded prevalence of gender dysphoria/incongruence increased substantially in children and young people between 2011 and 2021, particularly in recorded females. Levels of anxiety, depression and self-harm were high, indicating an urgent need for better prevention and treatment of mental health difficulties in these patients.
Prevalence of resistance-associated substitutions (RAS) in hepatitis C virus in the Former Soviet Union countries
Authors: Mustafa Aidana , Davlidova Salima , Abidi Syed Hani , Begimbetova Dinara , Heimer Robert , Vermund Sten H , Ali Syed
Published: January 2025

Objective

The emergence of resistance-associated substitutions (RASs) poses a significant challenge to the effective treatment of hepatitis C virus (HCV) infection using direct-acting antivirals. This study’s objective was to observe the prevalence of HCV genotypes and RAS within the Former Soviet Union (FSU) countries.

Methods

We analysed 60 NS3, 313 NS5A and 1119 NS5B sequences of HCV deposited in open-access databases from 11 FSU countries for the prevalence of genotypes and the presence of RAS using the Geno2Pheno software.

Results

The following NS3 RASs were revealed through our analyses: 156P/S/T, 168del, 80K, 55A and 174S. The most prevalent NS5A RAS was 30K (12.69%) in genotype 3a, associated with resistance to daclatasvir, elbasvir and ledipasvir, followed by 62S (8.96% in genotype 3a), linked with resistance to daclatasvir, and 93H (3.95% and 6.72% in genotypes 1b and 3a, respectively), conferring resistance to daclatasvir, ombitasvir, elbasvir, ledipasvir and velpatasvir. The NS5B RASs found in this study were 451S and 556G, associated with resistance to dasabuvir.

Conclusion

The high prevalence of HCV genotypes 1b and 3a in the FSU region and the presence of specific RASs should be considered when determining the most effective treatment regimen for HCV-infected individuals in the FSU countries.
Exploring the role of different coping styles in mediating the relationship between dyadic adjustment status and postpartum depression among postnatal women: a single-centre, cross-sectional study
Authors: Deng Jing , Chen Jing , Tan Yifei , Guo Xiujing , Liu Fan
Published: January 2025

Objectives

Postpartum depression (PPD) is a prevalent complication of childbearing, with numerous risk factors associated with its onset. Although the risk factors for PPD among postpartum women have been studied, the mechanisms underlying these factors remain inadequately understood. This study aimed to investigate the direct and mediating roles of different coping styles in the relationship between dyadic adjustment status and PPD among women 6 weeks postdelivery.

Design

Single-centre, cross-sectional study.

Setting

A tertiary care setting in Chengdu City, Sichuan Province, China, from July 2022 to January 2023.

Participants

The study involved 626 women 6 weeks post-delivery.

Outcome measures

The Dyadic Adjustment Scale, the Simplified Coping Style Questionnaire and the Edinburgh Postnatal Depression Scale (EPDS) were used to evaluate the dyadic adjustment status, coping styles and the depressive condition of postpartum women, respectively. Data analysis encompassed correlation and mediation analyses based on structural equation modelling.

Results

EPDS scores were significantly correlated with all four dimensions of dyadic adjustments status as well as with both positive and negative coping styles. Dyadic consensus (β= −0.16, p=0.005), affectional expression (β= −0.14, p=0.008) and dyadic cohesion (β= −0.10, p=0.037) directly correlated with PPD after adjusting for covariates. For dyadic satisfaction, the mediating effects of positive and negative coping styles on PPD were −0.04 (95% CI: −0.08 to –0.01) and −0.07 (95% CI: −0.11 to –0.03), respectively. Moreover, both positive and negative coping styles were identified as mediators in the relationship between dyadic cohesion and PPD, with mediating effects of −0.01 (95% CI: −0.03 to –0.00) and −0.09 (95% CI: −0.14 to –0.04), respectively. No mediation was found in the association between affectional expression and PPD.

Conclusion

Our findings suggest that both positive and negative coping styles mediate the relationship between dyadic adjustment status and PPD, especially concerning dyadic satisfaction and dyadic cohesion.