bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol and e-cigarette damage alveolar-epithelial barrier by activation of P2X7r and provoke brain endothelial injury via extracellular vesicles
Authors: Mekala Naveen , Trivedi Jayshil , Bhoj Priyanka , Togre Namdev , Rom Slava , Sriram Uma , Persidsky Yuri 
Published: January 2024

Abstract
Background
Use of nicotine containing products like electronic cigarettes (e-Cig) and alcohol are associated with mitochondrial membrane depolarization, resulting in the extracellular release of ATP, and mitochondrial DNA (mtDNA), mediating inflammatory responses. While nicotine effects on lungs is well-known, chronic alcohol (ETH) exposure also weakens lung immune responses and cause inflammation. Extracellular ATP (eATP) released by inflammatory/stressed cells stimulate purinergic P2X7 receptors (P2X7r) activation in adjacent cells. We hypothesized that injury caused by alcohol and e-Cig to pulmonary alveolar epithelial cells (hPAEpiC) promote the release of eATP, mtDNA and P2X7r in circulation. This induces a paracrine signaling communication either directly or via EVs to affect brain cells (human brain endothelial cells - hBMVEC).

Methods
We used a model of primary human pulmonary alveolar epithelial cells (hPAEpiC) and exposed the cells to 100 mM ethanol (ETH), 100 µM acetaldehyde (ALD), or e-Cig (1.75 µg/mL of 1.8% or 0% nicotine) conditioned media, and measured the mitochondrial efficiency using Agilent Seahorse machine. Gene expression was measured by Taqman RT-qPCR and digital PCR. hPAEpiC-EVs were extracted from culture supernatant and characterized by flow cytometric analysis. Calcium (Ca2+) and eATP levels were quantified using commercial kits. To study intercellular communication via paracrine signaling or by EVs, we stimulated hBMVECs with hPAEpiC cell culture medium conditioned with ETH, ALD or e-cig or hPAEpiC-EVs and measured Ca2+ levels.

Results
ETH, ALD, or e-Cig (1.8% nicotine) stimulation depleted the mitochondrial spare respiration capacity in hPAEpiC. We observed increased expression of P2X7r and TRPV1 genes (3-6-fold) and increased intracellular Ca2+ accumulation (20-30-fold increase) in hPAEpiC, resulting in greater expression of endoplasmic reticulum (ER) stress markers. hPAEpiC stimulated by ETH, ALD, and e-Cig conditioned media shed more EVs with larger particle sizes, carrying higher amounts of eATP and mtDNA. ETH, ALD and e-Cig (1.8% nicotine) exposure also increased the P2X7r shedding in media and via EVs. hPAEpiC-EVs carrying P2X7r and eATP cargo triggered paracrine signaling in human brain microvascular endothelial cells (BMVECs) and increased Ca2+ levels. P2X7r inhibition by A804598 compound normalized mitochondrial spare respiration, reduced ER stress and diminished EV release, thus protecting the BBB function.

Conclusion
Abusive drugs like ETH and e-Cig promote mitochondrial and endoplasmic reticulum stress in hPAEpiC and disrupts the cell functions via P2X7 receptor signaling. EVs released by lung epithelial cells against ETH/e-cig insults, carry a cargo of secondary messengers that stimulate brain cells via paracrine signals.
Evaluating spatially variable gene detection methods for spatial transcriptomics data
Authors: Chen Carissa , Kim Hani Jieun , Yang Pengyi 
Published: January 2024

Abstract
Background
The identification of genes that vary across spatial domains in tissues and cells is an essential step for spatial transcriptomics data analysis. Given the critical role it serves for downstream data interpretations, various methods for detecting spatially variable genes (SVGs) have been proposed. However, the lack of benchmarking complicates the selection of a suitable method.

Results
Here we systematically evaluate a panel of popular SVG detection methods on a large collection of spatial transcriptomics datasets, covering various tissue types, biotechnologies, and spatial resolutions. We address questions including whether different methods select a similar set of SVGs, how reliable is the reported statistical significance from each method, how accurate and robust is each method in terms of SVG detection, and how well the selected SVGs perform in downstream applications such as clustering of spatial domains. Besides these, practical considerations such as computational time and memory usage are also crucial for deciding which method to use.

Conclusions
Our study evaluates the performance of each method from multiple aspects and highlights the discrepancy among different methods when calling statistically significant SVGs across diverse datasets. Overall, our work provides useful considerations for choosing methods for identifying SVGs and serves as a key reference for the future development of related methods.
Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer: study protocol for a randomised controlled trial
Authors: Yu Liang , Shen Xiao-Juan , Liu He , Zhou Yu-Ting , Zhang Qin , Zhang Zhen-Duo , Shen Shu-Min 
Published: January 2024

Abstract
Background
A single injection of local anaesthetic (LA) in the erector spinae plane block (ESPB) can reduce pain after modified radical mastectomy (MRM) surgery, but the duration of analgesia is affected by the duration of the LA. The aim of this study is to investigate the effect of continuous ESPB on acute and chronic pain and inflammatory response after MRM surgery.

Methods
In this prospective, randomised, controlled trial, we will recruit 160 patients, aged 18–80 years, scheduled for elective MRM surgery under general anaesthesia. They will be randomly assigned to two groups: a continuous ESPB group (group E) and a sham block group (group C). Both groups of patients will have a nerve block (group C pretended to puncture) and an indwelling catheter fixed prior to surgery. Electronic pumps containing LA are shielded. The primary outcome is the total consumption of analgesic agents. The secondary outcomes include the levels of inflammation-related cytokines; the occurrence of chronic pain (post-mastectomy pain syndrome, PMPS); static and dynamic pain scores at 2, 6, 12, 24 and 48 h postoperatively; and post-operative and post-puncture adverse reactions.

Discussion
Analgesia after MRM surgery is important and chronic pain can develop when acute pain is prolonged, but the analgesic effect of a nerve block with a single injection of LA is limited by the duration of drug action. The aim of this trial is to investigate whether continuous ESPB can reduce acute pain after MRM surgery and reduce the incidence of chronic pain (PMPS), with fewer postoperative analgesic drug-related complications and less inflammatory response. Continuous ESPB and up to 12 months of follow-up are two innovations of this trial.

Trial registration
Chinese Clinical Trial Registry (https://www.chictr.org.cn/) ChiCTR2200061935. Registered on 11 July 2022. This trial is a prospective registry with the following registry names: Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer.
Comparison of hemostatic ability between spray coagulation and forced coagulation modes in endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for multicenter randomized controlled trial (Spray-G trial)
Authors: Maehara Kosuke , Esaki Mitsuru , Sumida Yorinobu , Yamaguchi Daisuke , Nishioka Kei , Homma Hitoshi , Inada Taisuke , Shiotsuki Kazuo , Fukuda Shin-Ichiro , Akiho Hirotada , Nomura Tadahiro , Mizuta Yumi , Ishida Satoshi , Fujimoto Shun , Kimura Shunichiro , Tanaka Yuichiro , Hata Kaori , Shiga Noriko , Iwasa Tsutomu , Kimura Yusuke , Nakamura Norimoto , Suzuki Yusuke , Minoda Yosuke , Hata Yoshitaka , Ogino Haruei , Tagawa Koshiro , Ihara Eikichi , Ogawa Yoshihiro 
Published: January 2024

Abstract
Background
Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD.

Methods
This multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study.

Discussion
This trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures.

Trial registration
The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009.
The Meteoritics Trial: efficacy of methotrexate after remission-induction with tocilizumab and glucocorticoids in giant cell arteritis—study protocol for a randomized, double-blind, placebo-controlled, parallel-group phase II study
Authors: Kreis Lena , Dejaco Christian , Schmidt Wolfgang Andreas , Németh Robert , Venhoff Nils , Schäfer Valentin Sebastian 
Published: January 2024

Abstract
Background
Glucocorticoids (GC) are the standard treatment for giant cell arteritis (GCA), even though they are associated with adverse side effects and high relapse rates. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, has shown promise in sustaining remission and reducing the cumulative GC dosage, but it increases the risk of infections and is expensive. After discontinuation of TCZ, only about half of patients remain in remission. Additionally, only few studies have been conducted looking at remission maintenance, highlighting the need for alternative strategies to maintain remission in GCA. Methotrexate (MTX) has been shown to significantly decrease the risk of relapse in new-onset GCA and is already a proven safe drug in many rheumatologic diseases.

Methods
This study aims to evaluate the efficacy and safety of MTX in maintaining remission in patients with GCA who have previously been treated with GC and at least 6 months with TCZ. We hypothesize that MTX can maintain remission in GCA patients, who have achieved stable remission after treatment with GC and TCZ, and prevent the occurrence of relapses. The study design is a monocentric, randomized, double-blind, placebo-controlled, parallel-group phase II trial randomizing 40 GCA patients 1:1 into a MTX or placebo arm. Patients will receive 17.5 mg MTX/matching placebo weekly by subcutaneous injection for 12 months, with the possibility of dose reduction if clinically needed. A 6-month follow-up will take place. The primary endpoint is the time to first relapse in the MTX group versus placebo during the 12-month treatment period. Secondary outcomes include patient- and investigator-reported outcomes and laboratory findings, as well as the prevalence of aortitis, number of vasculitic vessels, and change in intima-media thickness during the study.

Discussion
This is the first clinical trial evaluating remission maintenance of GCA with MTX after a previous treatment cycle with TCZ. Following the discontinuation of TCZ in GCA, MTX could be a safe and inexpensive drug.

Trial registration
ClinicalTrials.gov, NCT05623592. Registered on 21 November 2022.
EU Clinical Trials Register, 2022-501058-12-00.
German Clinical Trials Register DRKS00030571.
Inflammatory responses and barrier disruption in the trachea of chicks following Mycoplasma gallisepticum infection: a focus on the TNF-α-NF-κB/MLCK pathway
Authors: Zhong Lemiao , Wu Chunlin , Zhao Yan , Huang Baoqin , Luo Zhongbao , Wu Yijian 
Published: January 2024

AbstractMycoplasma gallisepticum (MG) can induce persistent inflammatory damage to the tracheal mucosa of poultry and cause chronic respiratory diseases in chickens. To further investigate the mechanism of MG-induced injury to the tracheal mucosa, we used chick embryo tracheal organ culture (TOC) as a model to study the invasion and reproduction of MG, the effect of MG on tracheal morphology, and the potential factors that promote MG tissue invasion. The results showed that MG infection significantly damaged the tracheal epithelial structure and weakened tracheal epithelial barrier function; MG also increased the occurrence of bacterial displacement, with a significant (p < 0.05) increase in the bacterial load of the infected TOCs at 5 and 7 days post-infection. In addition, MG significantly (p < 0.05) increased the expression levels of inflammatory cytokines, such as TNF-α, interleukin-1β (IL-1β), and IL-6, and activated the NF-κB signalling pathway, leading to increased nuclear translocation of NF-κB p65. Simultaneously, the map kinase pathway (MAPK) was activated. This activation might be associated with increased myosin light chain (MLC) phosphorylation, which could lead to actin-myosin contraction and disruption of tight junction (TJ) protein function, potentially compromising epithelial barrier integrity and further catalysing MG migration into tissues. Overall, our results contribute to a better understanding of the interaction between MG and the host, provide insight into the mechanisms of damage to the tracheal mucosa induced by MG infection, and provide new insights into the possible pathways involved in Mycoplasma gallisepticum infection in vivo.
Interventions to improve appropriateness of laboratory testing in the intensive care unit: a narrative review
Authors: Devis Luigi , Catry Emilie , Honore Patrick M. , Mansour Alexandre , Lippi Giuseppe , Mullier François , Closset Mélanie 
Published: January 2024

AbstractHealthcare expenses are increasing, as is the utilization of laboratory resources. Despite this, between 20% and 40% of requested tests are deemed inappropriate. Improper use of laboratory resources leads to unwanted consequences such as hospital-acquired anemia, infections, increased costs, staff workload and patient stress and discomfort. The most unfavorable consequences result from unnecessary follow-up tests and treatments (overuse) and missed or delayed diagnoses (underuse). In this context, several interventions have been carried out to improve the appropriateness of laboratory testing. To date, there have been few published assessments of interventions specific to the intensive care unit. We reviewed the literature for interventions implemented in the ICU to improve the appropriateness of laboratory testing. We searched literature from 2008 to 2023 in PubMed, Embase, Scopus, and Google Scholar databases between April and June 2023. Five intervention categories were identified: education and guidance (E&G), audit and feedback, gatekeeping, computerized physician order entry (including reshaping of ordering panels), and multifaceted interventions (MFI). We included a sixth category exploring the potential role of artificial intelligence and machine learning (AI/ML)-based assisting tools in such interventions. E&G-based interventions and MFI are the most frequently used approaches. MFI is the most effective type of intervention, and shows the strongest persistence of effect over time. AI/ML-based tools may offer valuable assistance to the improvement of appropriate laboratory testing in the near future. Patient safety outcomes are not impaired by interventions to reduce inappropriate testing. The literature focuses mainly on reducing overuse of laboratory tests, with only one intervention mentioning underuse. We highlight an overall poor quality of methodological design and reporting and argue for standardization of intervention methods. Collaboration between clinicians and laboratory staff is key to improve appropriate laboratory utilization. This article offers practical guidance for optimizing the effectiveness of an intervention protocol designed to limit inappropriate use of laboratory resources.
SLA-ORECS: an SLA-oriented framework for reallocating resources in edge-cloud systems
Authors: Lan Shizhan , Duan Zhuoxi , Lu Song , Tan Bin , Chen Shi , Liang Yeyu , Chen Shan 
Published: January 2024

AbstractThe emergence of the Fifth Generation (5G) era has ushered in a new era of diverse business scenarios, primarily characterized by data-intensive and latency-sensitive applications. Edge computing technology integrates the information services environment with cloud computing capabilities at the edge of the network. However, the evolving landscape of business models necessitates a unified edge architecture capable of accommodating diverse requirements, posing substantial challenges for service providers in meeting Service-Level Agreements (SLAs).In response to these challenges, we introduce SLA-ORECS. This innovative framework dynamically allocates dedicated and shared resources within the edge-cloud system to cater to service requests with varying SLAs, thereby facilitating performance isolation. Furthermore, we have developed an optimization algorithm to enhance the efficiency of SLA assurance during request dispatch.The evaluation of SLA-ORECS highlights its noteworthy performance improvements, particularly in terms of system throughput and average time consumption.
Consumer nutrition environment measurements for nutrient-dense food availability and food sustainability: a scoping review
Authors: Baker Katherine , Burd Laura , Figueroa Roger 
Published: January 2024

AbstractConsumer nutrition environments are defined as places in which consumers interact with the food they eat; these food choices can impact human and planetary health. Assessment measures for consumer nutrition environments are numerous, and vary widely on what, and how, they assess the food environment. The objective of this scoping review was to synthesize existing evidence on nutrition environment measurements and their capacity to assess nutrient-dense food access and food sustainability capacity. Eligibility criteria were developed to capture relevant peer-reviewed literature about auditing measures designed to assess nutrient-dense foods and food sustainability capacity in the consumer nutrition environment. A search strategy was conducted to collect articles published between January 1, 2002-June 4, 2022, using PubMed, Web of Science, Scopus, PsycINFO and the Cochrane library electronic databases. After screening 2457 manuscripts, 58 met inclusion criteria. Study aims, funding source(s), types of retailers assessed, assessment format and name, constructs measured, food categories measured, assessment of validity and/or reliability, and other relevant data were extracted from each manuscript. Results showed that most measures use checklists, surveys, questionnaires or similar methods to assess availability, quality, and price of select food items as assessment constructs. Most do not assess nutrient-dense food availability, and even fewer assess food sustainability. Development of comprehensive, reliable, and valid consumer nutrition environment measures that assess nutrient-dense food availability and food sustainability is important for research, planning, evaluation and advocacy aimed at improving consumer food environments for human and planetary health.
Factors associated with food security among small-holder farming households in Lesotho
Authors: Nkoko Nthabeleng , Cronje Natasha , Swanepoel Jan Willem 
Published: January 2024

Abstract
Background
Food insecurity and malnutrition are persistent challenges worldwide and Lesotho is not an exception. Hunger and poverty have worsened with the dawn of COVID-19 pandemic and on-going Russia–Ukraine war. The study seeks to assess food security and associated socio-economic factors among farming households in Lesotho. Household food security has been assessed using Household Food Access Scale (HFIAS) and Household Dietary Diversity Score (HDDS). Questionnaires were employed to collect data from 236 farming households.

Results
The HFIAS results show that 40% of the farming households were food secure, 18% were mildly food insecure, 32% were moderately food insecure and 10% were severely food secure and severe food insecurity mostly experienced in the highlands. HDDS results indicated that the farming households had consumed 8 to 12 food groups 7 days prior to data collection, the mean HDDS is 9.68. Households that are involved in commercial farming had more (9.98) diverse diets than those in subsistence farming (8.67). Households in the highlands have the lowest diet diversity (9.0) among the four agro-ecological zones. A logistic regression analysis indicated that the socio-economic factors associated with food security were household income, household size, marital status and education status of the respondent.

Conclusions
The findings depict that over half (60%) of the farming households experience varied degrees of food insecurity. Contrary to this, the farming households had consumed highly varied diets in the past 7 days. The socio-economic factors that influence the attainment of food security household food security were household size, household income, education and marital status. The findings suggest that agricultural development interventions must be more sensitive to household food security and nutrition, which includes training farmers on nutrition and food security issues. Furthermore, socio-economic factors must be considered in the development of interventions, since they influence the food security of the farming households.