bluuebunny/crossref_metadata_2025 huggingface dataset:
AAVone: A Cost-Effective, Single-Plasmid Solution for Efficient AAV Production with Reduced DNA Impurities
Authors: Yang Rongze , Tran Ngoc Tam , Chen Taylor , Cui Mengtian , Wang Yuyan , Sharma Tapan , Liu Yu , Zhang Jiantao , Yuan Xinxu , Zhang Danmeng , Chen Cuiping , Shi Zhen , Wang Leming , Dai Yuling , Zaidi Haniya , Liang Jiarui , Chen May , Jaijyan Dabbu , Hu Huan , Wang Bing , Xu Cheng , Hu Wenhui , Gao Guangping , Yu Daozhan , Tai Phillip W.L. , Wang Qizhao
Published: January 2025

Currently, the most common approach for manufacturing GMP-grade adeno-associated virus (AAV) vectors involves transiently transfecting mammalian cells with three plasmids that carry the essential components for production. The requirement for all three plasmids to be transfected into a single cell and the necessity for high quantities of input plasmid DNA, limits AAV production efficiency, introduces variability between production batches, and increases time and labor costs. Here, we developed an all-in-one, single-plasmid AAV production system, called AAVone. In this system, the adenovirus helper genes (E2A,E4orf6, andVA RNA), packaging genes (repandcap), and the vector transgene cassette are consolidated into a single compact plasmid with a 13-kb backbone. The AAVone system achieves a two- to four-fold increase in yields compared to the traditional triple-plasmid system. Furthermore, the AAVone system exhibits low batch-to-batch variation and eliminates the need for fine-tuning the ratios of the three plasmids, simplifying the production process. In terms of vector quality, AAVs generated by the AAVone system show similarin vitroandin vivotransduction efficiency, but a substantial reduction in sequences attributed to plasmid backbones and a marked reduction in non-functional snap-back genomes. In Summary, the AAVone platform is a straightforward, cost-effective, and highly consistent AAV production system – making it particularly suitable for GMP-grade AAV vectors.
Metagenomic estimation of absolute bacterial biomass in the mammalian gut through host-derived read normalization
Authors: Tang Gechlang , Carr Alex V. , Perez Crystal , Ramos Sarmiento Katherine , Levy Lisa , Lampe Johanna W. , Diener Christian , Gibbons Sean M.
Published: January 2025

Absolute bacterial biomass estimation in the human gut is crucial for understanding microbiome dynamics and host-microbe interactions. Current methods for quantifying bacterial biomass in stool, such as flow cytometry, qPCR, or spike-ins (i.e., adding cells or DNA from an organism not normally found in a sample), can be labor-intensive, costly, and confounded by factors like water content, DNA extraction efficiency, PCR inhibitors, and other technical challenges that add bias and noise. We propose a simple, cost-effective approach that circumvents some of these technical challenges: directly estimating bacterial biomass from metagenomes using bacterial-to-host (B:H) read ratios. We compare B:H ratios to the standard methods outlined above, demonstrating that B:H ratios are useful proxies for bacterial biomass in stool and possibly in other host-associated substrates. We show how B:H ratios can be used to track antibiotic treatment response and recovery in both mice and humans, which showed 403-fold and 45-fold reductions in bacterial biomass during antibiotic treatment, respectively. Our results indicate that host and bacterial metagenomic DNA fractions in human stool fluctuate longitudinally around a stable mean in healthy individuals, and the average host read fraction varies across healthy individuals by < 8-9 fold. B:H ratios offer a convenient alternative to other absolute biomass quantification methods, without the need for additional measurements, experimental design considerations, or machine learning algorithms, enabling retrospective absolute biomass estimates from existing stool metagenomic data.
Quantifying the spatiotemporal dynamics of the first two epidemic waves of SARS-CoV-2 infections in the United States
Authors: Lopes Rafael , Swartwood Nicole A. , Lan Yu , Chitwood Melanie H. , Klaassen Fayette , Salomon Joshua A. , Menzies Nicolas A. , Warren Joshua L. , Grubaugh Nathan D. , Cohen Ted
Published: January 2025

SARS-CoV-2 infection rates displayed striking temporal and spatial variation during the emergence of new variants globally and within the United States. While spatiotemporal “waves” of infection have been observed, quantitative assessments of their spread remain limited. Here, we estimate and compare the speed and spatial extent of the first two major infection waves in the United States, illustrating these dynamics through detailed visualizations. Our findings reveal that the origins of these waves coincide with large gatherings and the relaxation of masking mandates. Notably, the second wave spread more rapidly than the first, driven by multiple, non-contiguous origins of infection. This highlights the role of regional heterogeneity in epidemic dynamics and underscores the importance of localized public health measures in mitigating ongoing outbreaks.

Author Summary

Over the pandemic of SARS-CoV-2, efforts to identify and visualize the disease progression were made. However, quantitative visualization of the infections spreading are limited until today. Here we developed tools to visualize the spatial and temporal spreading of SARS-CoV-2 first two waves of infections over the Contiguous United States. We generated novels figures and movies that captures the dynamics of spreading and developed a new mapping of incidence of SARS-CoV-2 that goes below county-level. These outputs can help public health understanding and control efforts of the disease.
2-deoxy-D-glucose chemical exchange-sensitive spin-lock MRI of cerebral glucose metabolism after stroke in the rat
Authors: Boehm-Sturm Philipp , Schuenke Patrick , Foddis Marco , Mueller Susanne , Koch Stefan P. , Beard Daniel J. , Holloway Paul , Mottahedin Amin , Schröder Leif , Buchan Alastair M. , Mergenthaler Philipp
Published: January 2025

Rapid breakdown of cerebral glucose metabolism is a hallmark in stroke pathology. Metabolic activity delineates the penumbra from the infarct core, representing tissue that is potentially salvageable by therapeutic interventions. Tools to image dynamics of glucose and its spatial distribution could provide biomarkers of disease severity and of the success of therapeutic interventions.

Here, we developed a new protocol to measure glucose metabolism in a rat model of stroke using chemical exchange-sensitive spin-lock (CESL) MRI of the glucose analog 2-deoxy-D-glucose (2DG). We further implemented a protocol that combines 2DG-CESL-MRI with perfusion and diffusion MRI to relate this new signal to established definitions of hypoperfused tissue, cytotoxic edema and the penumbra. We found that 2DG-CESL-MRI provides a biomarker of disturbed glucose metabolism after stroke with high effect size. This is the first study to investigate CESL MRI of 2DG in the context of metabolism imaging in rodent stroke.
Genome-wide Viral Nascent RNA Sequencing Unveils Polymerase Pausing Landscape at Single-nucleotide Precision
Authors: Zhu Zhitong , Fung Cheuk Wang , Xu Xinzhou , Liang Zhibin , Gao Zhuoran , Wang Maggie Haitian , Li Mingyuan , Yeung Sin Yu , Wang Jiguang , Tse Carmen Ka Man , Cheung Peter Pak-Hang
Published: January 2025

Understanding viral replication and transcription mechanisms is critical for developing effective antiviral strategies. The study of viral gene regulation in host cellular environment is an important bridge for translating mechanistic discoveries fromin vitrostudies toin vivobut it remains stagnated due to the absence of technological advancement. Current methods for studying viral transcription and replication have been limited to capturing only the mature viral RNAs, obscuring the dynamic intermediates and mechanistic details of these crucial processes. Here, we introduce an original technology we called “Total Elongating Nascent VIral Polymerase single-molecule Sequencing (TenVIP-seq)”, which isolates and analyses newly synthesized RNA within the viral RNA-dependent RNA polymerase (RdRp) complex, enabling the discovery of mechanisms critical for both viral replication and transcription. Our first characterization of nascent RNA species for an RNA virus showed that RdRP exhibited non-random pausing with profile signatures along the eight influenza A virus (IAV) gene segments. We also revealed genome-wide pausing at known regulatory sites, such as the poly(U) tract polyadenylation site, and new putative regulatory sites at single-nucleotide resolution. Distinct pausing features between the viral genomic (vRNA) and anti-genomic (cRNA/mRNA) templates were observed, suggesting that RdRp processes transcription and replication differentially on positive and negative sense RNA. The NTP analog drug T-705 (favipiravir) intensified RdRp pauses during genome replication and transcription without introducing new pausing sites, while TRIM25 knockout in host cells infected with virus reduced RdRp pausing globally across the viral genome. Strikingly, we observed that terminal nucleotide misincorporations of nascent RNA sequencing of paused RdRP, which were previously undetectable, were as high as an average of 51.6% (vRNA) and 44.0% (cRNA/mRNA), suggesting that the mutational rate of viruses is much higher than previously thought. We demonstrated that TenVIP-seq holds potential in providing insights into the molecular mechanisms that control viral genome replication, gene expression and regulation, mutation, antiviral drug treatment, and virus-host interaction.
Crime of misappropriation of assets in the business context. A systematic review
Authors: Jimenez Serrano Jorge , Delgado Rodríguez María Jesús , Rodríguez Iglesias Isabel , López Pérez Rafael Manuel
Published: January 2025

Purpose

The purpose of this article is to deepen on the crime of assets misappropriation (AM) in the company, collecting through a systematic review of the published scientific literature those factors or theories that are being used when writing about this type of crime, as well as the implications for the business context.

Design/methodology/approach

The PRISMA methodology of systematic review has been used, from which 21 articles have been included, all of them published since 2005 in scientific journals related to the financial and economic context, but also to the criminological approach.

Findings

The articles provide several factors that are currently of interest in the study of the crime of AM in the company: the type of company in which this crime occurs, the most frequent types of AM, the elements of prevention used, as well as the profile and characteristics of employees who usually commit this type of crime.

Research limitations/implications

The conclusions of this article show the importance of studying this type of crime to combat it, not only because of the economic implications but also because of how it affects other spheres of the business context. The research has focused exclusively on articles written in English with the keyword “misappropriation assets”, which may have limited the inclusion of other articles of interest, although the objective of this study is precisely to evaluate the scientific interest in this specific type of Fraud.

Practical implications

Conclusions are drawn regarding prevention elements that are currently being used in the company to detect and combat this type of crime, as well as suggestions for future research.

Originality/value

This article seeks to support and encourage the study of this type of crime in business, following the sustainable development goals, which are the global goals designed to eradicate poverty, protect the planet and ensure global prosperity, among which is the promotion of business ethics and transparency in economic activities, for which the crime of misappropriation is a violation of these principles.
Perceiving and accessing resources in uncertain environments: insights from waste collection ventures in Burkina Faso
Authors: Dal Fior Catherine , Huybrechts Benjamin , Dufays Frédéric
Published: January 2025

Purpose

This article explores how waste collection venture founders in an uncertain sub-Saharan African environment perceive and access resources. More particularly, it investigates why, even in a similar context, different types of resource-mobilizing practices can be observed among venture founders and how these different practices can be related to founders’ diverging perceptions of resource accessibility.

Design/methodology/approach

The study compares seven waste collection ventures in Ouagadougou, Burkina Faso, a particularly uncertain market with shifting public regulation. The comparative case study analysis relies on interviews with venture founders, staff members and sector experts, as well as observations and archival data.

Findings

The findings suggest that the diverse approaches to resource accessibility can be associated with different ways in which venture founders perceive three key dimensions: environmental uncertainty (which is not necessarily seen as negative), the venture’s mission (for-profit or not-for-profit) and the founders’ self-perceptions. Three “perception-practice” patterns are identified, which illuminate different avenues for waste collection venture founders to access resources and position themselves in between local traditions and international influences.

Research limitations/implications

The findings contribute to refining the understanding of the links between entrepreneurial perceptions and resource access in uncertain environments, and further illuminate the diversity and complexity of entrepreneurial approaches in sub-Saharan Africa.

Practical implications

The findings of this paper may help waste management entrepreneurs better leverage resources and deal with uncertainty. Moreover, the paper includes recommendations to public authorities in charge of waste policy at the local, national and international levels, urging them to take the diversity of entrepreneurial approaches into consideration and formulate tailored policies to support waste entrepreneurs in accessing the resources they need.

Social implications

Informing the diversity of waste management practices and their effectiveness directly contributes to supporting small venture development and dealing with pollution, thereby addressing, respectively, sustainable development goals 8 (“Economic development and growth”) and 15 (“Life on land”).

Originality/value

As entrepreneurship in sub-Saharan Africa remains relatively underexplored in comparison with Western contexts, in particular from the perspective of entrepreneurial perceptions, the originality of this article is to connect resource access practices with the different perceptions unfolding in a similar context, thereby shedding light on how such diversity informs the understanding of entrepreneurial practices in uncertain contexts.
Unlocking the enigma of social commerce discontinuation: exploring the approach and avoidance drivers
Authors: Chong Sin-Er , Lim Xin-Jean , Ng Siew Imm , Kamal Basha Norazlyn
Published: January 2025

Purpose

This research explores the impact of approach and avoidance drivers on users’ discontinuance usage intention (DUI) in social commerce (s-commerce). It also examines the mediating role of perceived enjoyment and the moderating role of autotelic personality traits.

Design/methodology/approach

Using a purposive sample of 465 s-commerce users in Malaysia, data analysis was conducted using partial least squares structural equation modeling (PLS-SEM).

Findings

This study demonstrates that informational support is a key approach driver, enhancing perceived enjoyment and reducing perceived deception and DUI. Although perceived deception does not directly affect perceived enjoyment, it significantly predicts DUI. Additionally, the impact of informational support on DUI is mediated by perceived enjoyment and moderated by autotelic personality.

Practical implications

S-commerce stakeholders, including platform developers, sellers and policymakers, can leverage these findings to foster a sustainable s-commerce environment. Implementing the proposed strategies can enhance perceived enjoyment and reduce DUI among current users.

Originality/value

This research advances s-commerce marketing and IS discontinuance studies by extending the approach-avoidance motivations model (AAMM) into s-commerce and incorporating autotelic personality as a moderating factor provides new insights into user DUI in this evolving field.
Exploring the nexus between corporate social responsibility and consumer green behavior: the interplay of corporate image, service quality, customer trust and satisfaction
Authors: Liu HengYuan , Ma Sihan , AlWadi Belal Mahmoud , Alam Fahad , Zhang YueFeng
Published: January 2025

Purpose

In an era marked by growing environmental concerns, businesses are increasingly recognizing the importance of Corporate Social Responsibility (CSR) in influencing customer behavior, particularly in the context of sustainability and green practices. This paper aims to examine the impact of Corporate Social Responsibility (CSR) on Customer Green Behavior (CGB) through the mediating role of corporate image, service quality, customer trust and customer satisfaction.

Design/methodology/approach

A convenient sampling technique was employed to collect the data sample. A total of 741 questionnaires were distributed across four different hotel sectors in China. By using Structural Equation Modeling, the results suggest that CSR significantly influences CGB. Moreover, corporate image, service quality, customer trust and customer satisfaction show a partial mediating effect in the relationship between CSR and CGB.

Findings

The study findings suggest that the hotel industry should invest in CSR initiatives to enhance CGB by conducting pro-environmental activities. This study emphasizes how important CSR initiatives are in encouraging customers to adopt eco-friendly behavior. Overall, the results of this study extend the understanding of CSR, CGB, corporate image, service quality, customer trust and customer satisfaction in the context of the hotel industry and offer theoretical and managerial implications for developing and developed economies.

Originality/value

The originality value of this research lies in its comprehensive examination of the mediating effects of corporate image, service quality, customer trust and customer satisfaction on the relationship between CSR and CGB in the hotel industry. Furthermore, the study’s focus on the specific context of China adds novel insights to the existing literature on CSR and CGB. Discussions, limitations and research suggestions for future study are also provided.
Nitrogen content of herbarium specimens from arable fields and mesic meadows reflect the intensifying agricultural management during the 20th century
Authors: Kühn Paul , Umazekabiri Raymond , Römermann Christine , Bruelheide Helge , Wesche Karsten
Published: January 2025

Arable fields and mesic meadows have been affected by intensifying agricultural management and nutrient input during the 20th century, but direct evidence for the long‐term impact of intensification on plant nutrient contents remains scarce. Non‐destructive novel spectroscopic methods can produce such data from herbarium specimens, making it possible to investigate how contents of leaf nutrient traits, especially nitrogen and phosphorus, changed over the last century, and what role habitat type and management practices play.

We carried out a resurvey study of functional traits in arable field and mesic meadow communities. We used specimens from two German herbaria with a high coverage of their local floras: the herbaria Senckenberg Görlitz and Senckenberg Haussknecht in Jena. Following specimen information, the same plant species were resampled in the field in 2022 at the same locations. We employed near‐infrared spectroscopy to predict leaf nitrogen, phosphorus and carbon content of herbarium and field specimens. Nutrient content changes over time were compared with public records of regional P and N fertilization.

Overall, 1270 specimens of 76 species from both herbarium and field were studied, the oldest from the 19th century. Leaf nitrogen and the leaf nitrogen:phosphorus ratio increased significantly through time, while leaf phosphorus and carbon content decreased significantly over time. Arable field species showed a stronger response in leaf phosphorus content and leaf nitrogen:phosphorus ratio than mesic meadow species. The total amount of nitrogen or phosphorus fertilizer applied per year on a regional scale was found to be significantly correlated with the respective leaf nutrient content levels.

Synthesis: Our study shows a long‐term increase of leaf nitrogen in the studied habitats, paralleling increased chemical fertilizer applications in Germany. Our data indicate a shift from predominantly N‐limited towards more P‐limited growth conditions. The stronger response of species from arable fields compared to species from mesic meadows could indicate a faster adjustment to environmental pressures. This study thus also serves to showcase the potential of the combination of herbarium collections and NIR spectroscopy.
A Novel Lineage of Endosymbiotic Actinomycetales: Genome Reduction and Acquisition of New Functions in Bifidobacteriaceae Associated With Termite Gut Flagellates
Authors: Silva Joana Kästle , Hervé Vincent , Mies Undine S. , Platt Katja , Brune Andreas
Published: January 2025

Cellulolytic flagellates are essential for the symbiotic digestion of lignocellulose in the gut of lower termites. Most species are associated with host‐specific consortia of bacterial symbionts from various phyla. 16S rRNA‐based diversity studies and taxon‐specific fluorescence in situ hybridization revealed a termite‐specific clade of Actinomycetales that colonise the cytoplasm of Trichonympha spp. and other gut flagellates, representing the only known case of intracellular Actinomycetota in protists. Comparative analysis of eleven metagenome‐assembled genomes from lower termites allowed us to describe them as new genera of Bifidobacteriaceae. Like the previously investigated Candidatus Ancillula trichonymphae, they ferment sugars via the bifidobacterium shunt but, unlike their free‐living relatives, experienced significant genome erosion. Additionally, they acquired new functions by horizontal gene transfer from other gut bacteria, including the capacity to produce hydrogen. Members of the genus Ancillula (average genome size 1.56 ± 0.2 Mbp) retained most pathways for the synthesis of amino acids, including a threonine/serine exporter, providing concrete evidence for the basis of the mutualistic relationship with their host. By contrast, Opitulatrix species (1.23 ± 0.1 Mbp) lost most of their biosynthetic capacities, indicating that an originally mutualistic symbiosis is on the decline.
Insights Into Phylogeny, Diversity and Functional Potential of Poseidoniales Viruses
Authors: Prabhu Apoorva , Zaugg Julian , Chan Cheong Xin , McIlroy Simon J. , Rinke Chris
Published: January 2025

Viruses infecting archaea play significant ecological roles in marine ecosystems through host infection and lysis, yet they have remained an underexplored component of the virosphere. In this study, we recovered 451 archaeal viruses from a subtropical estuary, identifying 63 that are associated with the dominant marine order Poseidoniales (Marine Group II Archaea). Phylogenetic analyses of a subset of complete and nearly‐complete viral genomes assigned these viruses to the order Magrovirales, a lineage of Poseidoniales viruses, and identified a novel group of viruses distinct from Magrovirales. Utilising demarcation criteria established for the classification of archaeal tailed viruses, we propose two families within the order Magrovirales: Apasviridae (magrovirus group A), comprising the genera Agnivirus and Savitrvirus, and Krittikaviridae (magrovirus group E) encompassing the genus Velanvirus. Additionally, we propose a new order, distinct from Magrovirales, named Adrikavirales, which includes the genus Vyasavirus. Our detailed genomic characterisation of the new viral lineages revealed genes involved in viral assembly and egress, such as those responsible for creating holin rafts to lyse host cell membranes, a feature predominantly known from bacteriophages. Furthermore, we identified a broad spectrum of auxiliary metabolic genes, suggesting that these viruses can modulate host metabolism. Collectively, our findings substantially enhance the current understanding of the diversity and functional potential of Poseidoniales viruses.
Linear Plasmids in Micrococcus: Insights Into a Common Ancestor and Transfer by Conjugation
Authors: Perez María Florencia , Angelov Angel , Übelacker Maria , Torres Tejerizo Gonzalo Arturo , Farias María Eugenia , Liebl Wolfgang , Dib Julián Rafael
Published: January 2025

Actinobacteria have frequently been reported in the Andean Puna, including strains of the genus Micrococcus. These strains demonstrate resistance to high levels of UV radiation, arsenic, and multiple antibiotics, and possess large linear plasmids. A comparative analysis of the sequences and putative functions of these plasmids was conducted. The presence of large regions with high sequence identity (exceeding 30 kb in total) in all three studied Micrococcus megaplasmids indicates a clear evolutionary link among these elements. Genes related to essential plasmid functions were primarily found within these conserved regions, while genes associated with resistance to metals and antibiotics resided in accessory regions. Moreover, the abundance of open reading frames related to transposition and recombination, along with local deviations from the average GC content, provides evidence for the mosaic nature and considerable genetic plasticity of these plasmids. This study presents evidence of a common ancestor for linear plasmids in Micrococcus and suggests that horizontal gene transfer likely occurs frequently within Andean lakes, providing the native microbial community with a beneficial gene pool to withstand extreme conditions. Additionally, the successful transfer of the linear plasmid pLMA1 by a DNase‐insensitive, conjugation‐type mechanism and its potential use as a genetic vector is demonstrated.
Silent Suffering: Using Machine Learning to Measure CEO Depression
Authors: CHENG SUNG‐YUAN (MARK) , GOLSHAN NARGESS M.
Published: January 2025

We introduce a novel measure of CEO depression by applying machine learning models that analyze vocal acoustic features from CEOs' conference call recordings. Our research was preregistered via the Journal of Accounting Research's registration‐based editorial process. In this study, we validate this measure and examine associated factors. We find that greater firm risk is positively associated with CEO depression, whereas higher job demands are negatively associated with CEO depression. Female and older CEOs show a lower likelihood of depression. Using this novel measure, we then explore the relationship between CEO depression and career outcomes. Although we do not find any evidence that CEO depression is associated with CEO turnover, we find some evidence that turnover‐performance sensitivity is higher among depressed CEOs. We also find limited evidence of higher compensation and higher pay‐performance sensitivity for depressed CEOs. This study provides new insights into the relationship between CEO mental health and career outcomes.
Lymph Node Metastasis for pN+ Superficial Esophageal Squamous Cell Carcinoma
Authors: Yang Yafan , Xue Liyan , Chen Xiankai , Kang Mingqiang , Zhang Renquan , Tian Hui , Ma Jianqun , Fu Maoyong , Wei Jinchang , Liu Qi , Hao Anlin , He Yi , Zhang Ruixiang , Xie Hounai , Xu Lei , Luo Peng , Qin Jianjun , Li Yin
Published: January 2025

Objectives

This study aimed to analyze lymph node metastasis (LNM) distribution in superficial esophageal squamous cell carcinoma (ESCC) and its impact factors on survival.

Methods

We reviewed 241 pT1N+ ESCC cases between February 2012 and April 2022 from 10 Chinese hospitals with a high volume of esophageal cancer (EC). We analyzed clinicopathological data to identify overall survival (OS) risk factors and LNM distribution in relation to tumor invasion depth.

Results

Of the 241 patients, 26 (10.8%) had pT1a cancer and 215 (89.2%) had pT1b cancer. We showed that N3 stage, ≤ 28 lymphadenectomies, and nerve infiltration (NI) were negative factors for OS in superficial pN+ ESCC, whereas the OS was not definitively affected by the tumor depth and the choice of adjuvant therapy. In general, the LNM rates of the 193 pT1N+ ESCC cases can be ranked in the following order: station 106recR > station 106recL > station 1 > station 7 > station 2. With deeper tumor invasion, the higher LNM rate was observed near the bilateral recurrent laryngeal nerves (RLN), but there was no statistically significant difference.

Conclusions

In superficial ESCC, LNM was frequently observed along the 106recR (35.8%) and 106recL (25.6%) stations. Advanced N‐staging (N3) was a major negative impact factor in prognosis, and adequate lymph nodes dissected (LND) (N > 28) improved OS of pT1N+ ESCC. However, in superficial ESCC, tumor infiltration depth did not affect patients' OS or the distribution of positive LNs. The optimal adjuvant treatment that favors survival for these patients required further investigation.
Proteomic Analysis of Plasma Exosomes Enables the Identification of Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease
Authors: Zhang Huohuo , Wu Jiaxuan , Gan Jiadi , Wang Wei , Liu Yi , Song Tingting , Yang Yongfeng , Ji Guiyi , Li Weimin
Published: January 2025

Chronic obstructive pulmonary disease (COPD) is confirmed as an independent risk factor for the development of lung cancer. Although low‐dose CT screening significantly reduces the mortality rate of lung cancer, the misdiagnosis and missed diagnosis rates remain high in the COPD population. Additionally, several COPD patients are unable to undergo invasive histological examinations. Therefore, there is an urgent need for minimally invasive biomarkers to screen or diagnose lung cancer in COPD patients. In this study, peripheral blood samples were collected from COPD patients with and without lung cancer. Plasma exosomes (EVs) were extracted for proteomic analysis. Sixteen differentially expressed proteins (DEPs) were preliminarily selected via label‐free quantification (LFQ) proteomic technology and comprehensive bioinformatics analysis. Parallel reaction monitoring (PRM) targeted validation identified five candidate proteins associated with COPD with lung cancer. Compared to the COPD group, KRT1, KRT9, and KRT10 were significantly upregulated in the COPD with lung cancer group, while GPLD1 and TF were downregulated. The biomarkers identified in our study provide a foundation for non‐invasive screening and diagnosis of lung cancer in COPD patients and exploration of the mechanisms shared between COPD and lung cancer.
Efficacy of Corticosteroids in Patients With Recurrent Pregnancy Loss: A Systematic Review and Meta‐Analysis
Authors: D'Ippolito Silvia , Gavi Filippo , Granieri Chiara , De Waure Chiara , Giuliano Sara , Cosentino Francesco , Tersigni Chiara , Scambia Giovanni , Di Simone Nicoletta
Published: January 2025

Recurrent pregnancy loss (RPL) represents a complication of pregnancy occurring in 1%–3% of all couples trying to conceive. About 50%–60% of RPL cases remain idiopathic, therefore therapeutic strategies seem empirical and based on unproven evidence. We investigated the efficacy of corticosteroids in women with RPL. We conducted a systematic review and meta‐analysis, up to August 2024, in the PubMed, Scopus, and Web of Science databases, including studies on idiopathic RPL women and comparing corticosteroids versus control treatment. Primary outcome was the ongoing pregnancy rate beyond 12 weeks of gestation; secondary outcomes were live birth rate (LBR), stillbirth, birth weight, incidence of preeclampsia and/or gestational diabetes, gestational age at delivery, and fetal abnormalities. Four studies comprising 417 RPL women randomly assigned to steroid or control treatment were included. We found that oral corticosteroids significantly increase the ongoing pregnancy rate beyond 12 weeks of gestation compared to the control group (log OR [odds ratio] = 1.49 [0.32, 2.67], p = 0.01), with high heterogeneity (I2 = 75%), and improve LBR (log OR = 0.9 [0.11, 1.69], p = 0.03), with low heterogeneity (I2 = 0.05%). However, the limited number of studies significantly limits the strength of the findings. Also, the benefit/risk assessment of the use of corticosteroids in early pregnancy for RPL is still unclear.
FOXL2 Knockdown Inhibits the Progression of Endometriosis
Authors: Zhang Bing , Li Shang‐Jin , Yuan Hua , Cong Shan‐Shan , Zhao Shao‐Jie , Yang Xiao‐Jun
Published: January 2025

Problem

Endometriosis (EM) is known as a common estrogen‐dependent chronic inflammatory disease. Elevated levels of Forkhead box L2 (FOXL2) have been observed in uterine diseases, including EM. However, the molecular mechanism of FOXL2 in EM needs to be further illustrated. This study aimed to investigate the regulatory role of FOXL2 in EM rats and isolated ectopic endometrial stromal cells (EC‐ESCs).

Method of Study

FOXL2 knockdown were designed to evaluate the effects of FOXL2 in EM model rats and EC‐ESCs. Hematoxylin‐eosin (HE) staining was used to evaluate the pathological morphology of ectopic endometrium. Reverse transcriptase quantitative polymerase chain reaction (RT‐qPCR) analysis and immunohistochemistry (IHC) were applied to detect the expression of FOXL2, EM‐related genes, and epithelial to mesenchymal transition‐related proteins. The proliferation, migration, invasion, and apoptosis of EC‐ESCs were determined by 5‐ethynyl‐2′‐deoxyuridine (EDU) assay, Transwell assay, and flow cytometry.

Results

The FOXL2 level was remarkably higher in the ectopic endometrial tissue than that in the normal endometrial tissue. Knockdown of FOXL2 notably improved the pathological morphology of EM in rats, and decreased expression levels of ER‐α, ER‐ß, and Cyp19a. Additionally, down‐regulation of FOXL2 suppressed cells proliferation, migration and invasion, and stimulated more apoptotic cells in EC‐ESCs. Besides, FOXL2‐small interfering RNA (FOXL2‐siRNA) treatment resulted in enhanced cleaved‐Caspase3 protein expression and cleaved‐Caspase3/Caspase3 ratio in EC‐ESCs.

Conclusion

FOXL2 participates in the occurrence and development of EM through promoting epithelial‐mesenchymal transition procession and enhancing the migration and invasion of EC‐ESCs, suggesting that FOXL2 may be a new therapeutic target for the EM therapy.
Immunotherapy on ICU: a narrative review
Authors: Carter Sef , Wigmore Timothy
Published: January 2025

Background

Patients with cancer account for 15% of all admissions to critical care and so an understanding of the pathophysiology and anticipated complications of specialist treatment is essential for the intensive care clinician. The development of chimeric antigen receptor T‐cell therapy for haematological malignancies and immune checkpoint inhibitors for solid organ tumours has led to significant improvements in the prognosis of those patients whose tumours respond. This review is intended to provide the non‐specialist with an understanding of the current concepts in pathophysiology, diagnosis and management of complications due to chimeric antigen receptor T‐cell therapy and immune checkpoint inhibitors for malignant disease.

Methods

We performed searches of electronic databases to identify relevant peer‐reviewed publications in the literature. Basic science; clinical trials; cohort studies; systematic reviews; meta‐analyses; and guidelines were eligible for inclusion. Abstracts were screened to identify publications relevant to immune effector cell toxicities of chimeric antigen receptor T‐cell therapy and immune‐related adverse events of immune checkpoint inhibitors.

Results

While the pathophysiology for toxicities due to chimeric antigen receptor T‐cells and immune checkpoint inhibitors remains incompletely understood, targeted drug therapies have been successfully implemented for toxicities such as cytokine release syndrome. Corticosteroids remain an important component of pharmacological management. The diagnosis of toxicities remains largely clinical, and a high index of suspicion should remain for infective complications. Management of toxicities should be undertaken in conjunction with the patient's primary oncologist.

Conclusion

Despite significant advances in the development of targeted immunotherapy, the mechanism of action for the resultant toxicities remains poorly understood and limits the development of predictive models, diagnostic biomarkers and highly effective treatment options. Further research is needed to identify treatment regimens which minimise the use of corticosteroids in chimeric antigen receptor T‐cell and immune checkpoint inhibitor‐associated toxicities.
The inequalities and challenges of prehabilitation before cancer surgery: a narrative review
Authors: Stewart Hilary , Stanley Sophie , Zhang Xiubin , Ashmore Lisa , Gaffney Christopher , Rycroft‐Malone Jo , Smith Andrew F. , Wareing Laura , Shelton Cliff
Published: January 2025

Introduction

Prehabilitation seeks to enhance functional capacity and preparedness before surgery with the aim of improving outcomes; it is generally based on exercise, diet and psychological interventions. While there is obvious appeal to this approach in terms of patient experience and resource use, the interventions are complex and the evidence base for prehabilitation before cancer surgery is heterogeneous. Prehabilitation requires patient understanding and motivation as well as commitment of resources. Programmes are challenging to design and implement, and can generate ‘intervention‐based inequalities’ based on the capacity of patients to engage. We present a narrative review on the inequalities and challenges of prehabilitation before cancer surgery.

Methods

We searched databases of peer‐reviewed research to identify appropriate articles. We used the results in combination with iterative searches based on citation tracking, grey literature (e.g. patient information resources) and articles from personal libraries, to develop our discussion.

Results

We describe the uncertainties in the evidence base for prehabilitation before cancer surgery, and the challenges and barriers for healthcare providers, systems and patients. Key findings include that prehabilitation is under‐researched in many cancers and that people with lower health literacy, from minority ethnic groups and socio‐economically disadvantaged backgrounds, are less likely to engage, despite often having worse peri‐operative outcomes.

Discussion

Prehabilitation must be implemented carefully to avoid widening inequalities. More research is needed, both in terms of the impact of interventions and to understand how prehabilitation should account for the social determinants of health.
Causes and management of acute oncological pain: a narrative review
Authors: Laycock Helen , Ramdin Candice , Grayer Justin , Brown Matthew R. D.
Published: January 2025

Introduction

Acute pain in cancer is an important but often overlooked feature of many patients' oncological journey. Cancer‐related pain is associated commonly with more persistent pain states caused by both the disease and its treatment, but there are numerous causes of acute pain which can develop in patients with cancer. This pain is frequently severe, can be challenging to manage and its suboptimal control can directly impact on oncological outcomes. This narrative review provides an overview of several causes of acute pain in patients with cancer and management approaches.

Methods

A focused literature review was conducted to encompass the search terms ‘acute pain’, ‘oncology’ and ‘cancer’ in adult and paediatric populations.

Results

Acute pain is common in patients with cancer with a number of pain generators identified. Broadly, these are disease‐ and treatment‐related but commonality in pain mechanisms and features are present. Importantly, these pain states do not occur in isolation; a patient may experience multiple acute pain episodes during their oncology journey.

Discussion

As the oncological treatment landscape shifts and increasing numbers of novel treatments are employed, the number of causes of acute pain in patients with cancer rises. This pain is often managed by non‐pain specialists and suboptimal control has a variety of deleterious effects. It is important that awareness of acute pain in the oncological population is increased and treatment approaches, which adopt a biopsychosocial structure, are optimised.
Postnatal cytomegalovirus infections did not alter amplitude‐integrated electroencephalography signals or general movements in preterm infants
Authors: Neubauer Vera , Gande Nina , Winkler Ira , Posod Anna , Schreiner Christina , Hammerl Marlene , Kiechl‐Kohlendorfer Ursula , Griesmaier Elke
Published: January 2025

Aim

Controversy prevails about whether postnatal cytomegalovirus (CMV) infections are associated with adverse neurodevelopmental outcomes. We aimed to investigate whether amplitude‐integrated electroencephalography (aEEG) signals and General Movement Assessment (GMA) scores differed in very preterm infants with postnatal CMV infections.

Methods

This was a retrospective single‐centre study, conducted at Innsbruck Medical University Hospital, Austria, between February 2011 and November 2018. We screened 461 infants born before 32 weeks of gestation for CMV infections. Their aEEG signals were analysed for the distribution of background activity patterns and their total maturation scores and component scores. The GMA was performed at 36 weeks of postmenstrual age, term‐equivalent age and 3 months of corrected age.

Results

We studied 20 infants (55% male) with postnatal CMV infections, born at a mean gestational age of 28.1 (25.3–30.7) weeks and a mean birth weight of 1064 (640–1600) grams. No differences were found in the aEEG signals or GMA scores between these infants and 441 uninfected controls.

Conclusion

Preterm infants with postnatal CMV infections showed no alterations in neonatal aEEG signals or GMA scores, compared with the uninfected controls. Longer follow‐up studies are needed to evaluate the effect of postnatal cytomegalovirus infections on later neurodevelopmental outcomes.
Work alienation through the dialectical lens
Authors: Liu Juanjuan , Carminati Lara , Wilderom Celeste
Published: January 2025

Work alienation (WA) is on the rise, especially in today's era of globalization and digitalization. However, its foundational ties to Marx and Hegel's conceptualizations are often overlooked. Despite extensive scholarly examination across disciplines, the conceptualization of WA remains plagued by a lack of consensus concerning its definitions, processes, and operationalizations. This systematic literature review identifies four major definitional approaches and their inherent limitations. First, equating WA with its antecedents diverts attention from its core mechanisms. Second, definition‐by‐negation leads to an underspecified construct, raising questions about empirical congruence. Third, defining WA through its correlates risks confusing it with different concepts. Fourth, expanding the construct of WA, to include distant constructs with surplus meanings, camouflages WA's essence, hindering a deeper understanding of the phenomenon. To enhance conceptual clarity, this paper aims to clarify WA's definitions, measurements, guiding theories, triggers, ramifications, and coping strategies within organizational contexts. Drawing from Hegel and Marx's dialectical lens, we compose a definition centered on a three‐faceted self‐other dialectic. Also, we present a three‐stage developmental model, illustrating how WA develops and manifests itself as the relationships among the self, others, and work‐life contexts evolve. By integrating elements from various management theories, we offer a fresh perspective for new research aimed at preventing WA. By addressing the theoretical and practical challenges that may arise, we emphasize the crucial role of Human Resource Management and team leaders in recognizing and mitigating WA to preserve vital individual, team, organizational and societal resources.
Impedance measurement for nondestructive venison pH estimation using touch‐type electrodes
Authors: Igarashi Akari , Muramoto Takayuki
Published: January 2025

The pH of venison is affected by deer capture methods, which affects its water‐holding capacity (WHC) during heating. Therefore, cooking or processing venison requires careful consideration of WHC at different pH levels. While this requires nondestructively measuring the pH of venison during distribution, there are no established methods to nondestructively distinguish between normal‐ and high‐pH meats. We investigated the relationship between the pH of venison and impedance measured with touch‐type electrodes. Significant negative correlations were found between pH before and after storage and drip loss (p < 0.05) and between impedance before storage using touch‐type electrodes measured at 10 kHz and pH after 24 h of storage (p < 0.01). These results provided an estimating equation (y = −0.10x + 10.84) that can be used to nondestructively determine the pH of venison (y) after 24 h of storage by measuring its impedance (x) before storage using touch‐type electrodes measured at 10 kHz (p < 0.01). Therefore, this study suggests the possibility of nondestructively estimating venison pH by measuring impedance using touch‐type electrodes.
Longitudinal split fracture of the lateral malleolus causing tarsocrural subluxation in a Siberian Husky
Authors: Kolichis JM
Published: January 2025

A 4‐year‐old Siberian Husky was referred for bilateral hock trauma after being involved in a road traffic accident. The dog sustained a grade 3 shearing injury to the medial right hock with tibiotarsal subluxation, which was managed with a transarticular frame. The left hock sustained a rare open longitudinal split fracture of the lateral malleolus, resulting in lateral tarsocrural instability. The fracture was repaired directly with cross pins and a figure‐of‐eight tension band wire, which restored joint congruency and stability. All implants were removed after 8 weeks. The dog had a good functional outcome at 8‐month follow‐up. Based on a search of the veterinary literature, this is the first published report of such a lateral malleolar fracture configuration in dogs.