bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of clinical decision support on controlled substance prescribing
Authors: Seymour Rachel B. , Wally Meghan K. , Hsu Joseph R. ,   PRIMUM Group, Beuhler Michael , Bosse Michael J. , Gibbs Michael , Griggs Christopher , Jarrett Steven , Leas Daniel , Odum Susan , Roomian Tamar , Runyon Michael , Saha Animita , Schiro Sharon , Sullivan D. Matthew , Watling Brad , Wyatt Stephen , Yu Ziqing 
Published: October 2023

Abstract
Background
Prescription drug overdose and misuse has reached alarming numbers. A persistent problem in clinical care is lack of easy, immediate access to all relevant information at the actionable time. Prescribers must digest an overwhelming amount of information from each patient’s record as well as remain up-to-date with current evidence to provide optimal care. This study aimed to describe prescriber response to a prospective clinical decision support intervention designed to identify patients at risk of adverse events associated with misuse of prescription opioids/benzodiazepines and promote adherence to clinical practice guidelines.

Methods
This study was conducted at a large multi-center healthcare system, using data from the electronic health record. A prospective observational study was performed as clinical decision support (CDS) interventions were sequentially launched (January 2016–July 2019). All data were captured from the medical record prospectively via the CDS tools implemented. A consecutive series of all patient encounters including an opioid/benzodiazepine prescription were included in this study (n = 61,124,172 encounters; n = 674,785 patients). Physician response to the CDS interventions was the primary outcome, and it was assessed over time using control charts.

Results
An alert was triggered in 23.5% of encounters with a prescription (n = 555,626). The prescriber decision was influenced in 18.1% of these encounters (n = 100,301). As the number of risk factors increased, the rate of decision being influenced also increased (p = 0.0001). The effect of the alert differed by drug, risk factor, specialty, and facility.

Conclusion
The delivery of evidence-based, patient-specific information had an influence on the final prescription in nearly 1 in 5 encounters. Our intervention was sustained with minimal prescriber fatigue over many years in a large and diverse health system.
Versatile generation of precise gene edits in bovines using SEGCPN
Authors: Wang Ming , Ding Fangrong , Wang Haiping , Li Ling , Dai Yunping , Sun ZhaoLin , Li Ning 
Published: October 2023

Abstract
Background
Gene knockout and knock-in have been widely performed in large farm animals based on genome editing systems. However, many types of precise gene editing, including targeted deletion, gene tagging, and large gene fragment replacement, remain a challenge in large farm animals.

Results
Here, we established versatile self-excising gene-targeting technology in combination with programmable nucleases (SEGCPN) to efficiently generate various types of precise gene editing in bovine. First, we used this versatile method to successfully generate bovine embryos with point mutations and 11-bp deletions at the MSTN locus. Second, we successfully generated bulls with EGFP labeling at the SRY locus. Finally, we successfully generated humanized cows in which the endogenous 18-kb α-casein gene was replaced with a 2.6-kb human α-lactalbumin gene.

Conclusions
In summary, our new SEGCPN method offers unlimited possibilities for various types of precise gene editing in large animals for application both in agriculture and disease models.
Circulating chemerin levels in preeclampsia: a systematic review and meta-analysis
Authors: Yin Yangxue , Xie Shuangshuang , Xu Qin , Liao Lingyun , Chen Hongqin , Zhou Rong 
Published: October 2023

Abstract
Background
Preeclampsia (PE) is a new-onset pregnancy-specific disorder with a high prevalence that leads to over 70 000 maternal and 500 000 foetal fatalities worldwide each year. The level of chemerin, a newly identified adipokine, is increased in diabetic and obese patients. Currently, there are several studies describing the relationship between maternal circulating chemerin levels and PE. Therefore, this study aimed to assess their association in pooled samples.

Methods
Four databases were systematically searched to identify potential studies that reported circulating chemerin levels in PE and normal pregnancy groups. Standardized mean differences (SMDs), 95% confidence intervals (CIs), and 95% prediction intervals (PIs) were calculated using a random-effects meta-analysis. The probability of heterogeneity was also investigated by sensitivity analysis, subgroup analysis, and meta-regression.

Results
Thirteen studies in 11 articles with a total of 860 PE patients and 1309 women with normal pregnancies met the inclusion criteria. The results of the meta-analysis revealed that circulating chemerin, which levels in PE patients were considerably higher than those in controls (SMD = 1.39, 95% CI: 1.02, 1.77, 95% PI: -0.07, 2.86). Moreover, sensitivity analysis determined that the outcomes of the overall pooled results were not affected after the elimination of any study. Notably, subgroup analysis demonstrated a similar expression pattern irrespective of geographic location, severity, timing of sampling, and sample size. Last, there were no factors that significantly impacted the overall estimate, according to meta-regression.

Conclusions
This meta-analysis is the first to assess circulating chemerin levels in PE patients. The findings indicate that circulating chemerin levels may be a potential marker to diagnose PE.
IgG immune complex-induced acute lung injury is ameliorated by cAMP via down-regulation of C/EBP- and AP-1-mediated transcriptions
Authors: Yan Chunguang , Chen Jing , Tang Huifang , Deng Chunmin , Zhang Qi , Wang Ximo 
Published: October 2023

Abstract
Background
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are life threatening pulmonary diseases, and we are now lack of effective therapeutic methods. Inflammatory responses are essential for initiating ALI/ARDS. Thus, ameliorating inflammatory reaction might be beneficial for treatment of the disease. There are increasing data that phosphodiesterase-4 (PDE4)-selective inhibitors, which may elevate cellular cyclic adenosine 3′, 5′-monophosphate (cAMP) level, could suppress inflammation. However, whether they could be used to treat IgG immune complex (IgG-IC)-associated ALI has not been determined.

Methods
ALI is induced by treating mice with airway deposition of IgG immune complexes. Cellular cAMP concentrations are elevated by treating mice or macrophages with Rolipram/Roflumilast. The degree of pulmonary injury is reflected by lung permeability, leukocyte accumulation, histological change and expressions of pro-inflammatory mediators. 6-Bnz-cAMP and H-89 are used to regulate protein kinase A (PKA) activity, and 8-pCPT-2′-O-Me-cAMP is applied to activate exchange proteins directly activated by cAMP (Epac). Gene expressions are analyzed by real-time PCR, ELISA or Western blot. CCAAT/enhancer binding protein (C/EBP) and activation protein 1 (AP-1) transcription activities are estimated by measuring the luciferase productions.

Results
IgG-IC-induced ALI is attenuated by the PDE4-selective inhibitor, which is due to reduced expressions of cytokine and chemokines. Interestingly, we find that cAMP downstream effector molecule PKA but not Epac is involved in negative regulation of IgG-IC-mediated pro-inflammatory mediators’ productions. Mechanistically, activation of cAMP-PKA signal axis leads to inactivation of MAPK pathway, resulting in a decrease in C/EBP- and AP-1-mediated transcriptions of pro-inflammatory mediators.

Conclusions
Our data demonstrate, for the first time, that cAMP-PKA signal is involved in down-regulation of IgG-IC-associated inflammatory responses via down-regulating MAPK activation, which is critical for transcriptional activities of C/EBP and AP-1. Collectively, our experiments provide theoretical base for the potential application of PDE4-selective inhibitor to clinic for treatment of IgG-IC-related acute lung injury.
Insights from the scale-up and implementation of the Deadly Liver Mob program across nine sites in New South Wales, Australia, according to the RE-AIM framework
Authors: Cama Elena , Beadman Kim , Beadman Mitch , Walker Melinda , Treloar Carla 
Published: October 2023

Abstract
Background
The Deadly Liver Mob (DLM) program is a peer-led health promotion program that aims to improve access to screening and treatment for blood borne viruses and sexually transmissible infections for Aboriginal and Torres Strait Islander Australians. In this paper, we used client and staff insights to explore the successes and challenges of implementing the DLM program according to the RE-AIM framework, which explores real-world implementation of interventions according to reach, effectiveness, adoption, implementation, and maintenance.

Methods
Clients and staff were recruited through the DLM program. Semi-structured interviews were conducted with four Aboriginal and Torres Strait Islander and 11 non-Aboriginal or Torres Strait Islander health workers, as well as 33 Aboriginal and Torres Strait Islander clients of the program.

Results
Findings show the positive effects of the DLM program, in creating a culturally safe and sensitive environment for Aboriginal and Torres Strait Islander clients to access care. In particular, the employment of frontline Aboriginal and Torres Strait Islander workers to deliver the education was touted as one of the primary successes of the program, in enabling workers to build trust between clients and mainstream health systems, which has the flow on effect of encouraging clients to go through to screening. The use of the RE-AIM framework illustrates the challenges of implementing real-world interventions across various locations, such as the difficulties in delivering DLM in regional and remote areas due to covering large geographic areas with minimal public transport available.

Conclusions
The data emphasise the need for interventions to be adaptable and flexible, altering elements of the program to suit local and community needs, such as by offering mobile and outreach services to enable access across regional and rural areas. The findings of this evaluation have been used to develop tools so that the learnings from DLM can be shared with others who may be hoping to implement DLM or other similar programs.
Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in mice
Authors: Schmid Anna Marlene , Razim Agnieszka , Wysmołek Magdalena , Kerekes Daniela , Haunstetter Melissa , Kohl Paul , Brazhnikov Georgii , Geissler Nora , Thaler Michael , Krčmářová Eliška , Šindelář Martin , Weinmayer Tamara , Hrdý Jiří , Schmidt Katy , Nejsum Peter , Whitehead Bradley , Palmfeldt Johan , Schild Stefan , Inić-Kanada Aleksandra , Wiedermann Ursula , Schabussova Irma 
Published: October 2023

Abstract
Background
E. coli O83 (Colinfant Newborn) is a Gram-negative (G-) probiotic bacterium used in the clinic. When administered orally, it reduces allergic sensitisation but not allergic asthma. Intranasal administration offers a non-invasive and convenient delivery method. This route bypasses the gastrointestinal tract and provides direct access to the airways, which are the target of asthma prevention. G- bacteria such as E. coli O83 release outer membrane vesicles (OMVs) to communicate with the environment. Here we investigate whether intranasally administered E. coli O83 OMVs (EcO83-OMVs) can reduce allergic airway inflammation in mice.

Methods
EcO83-OMVs were isolated by ultracentrifugation and characterised their number, morphology (shape and size), composition (proteins and lipopolysaccharide; LPS), recognition by innate receptors (using transfected HEK293 cells) and immunomodulatory potential (in naïve splenocytes and bone marrow-derived dendritic cells; BMDCs). Their allergy-preventive effect was investigated in a mouse model of ovalbumin-induced allergic airway inflammation.

Results
EcO83-OMVs are spherical nanoparticles with a size of about 110 nm. They contain LPS and protein cargo. We identified a total of 1120 proteins, 136 of which were enriched in OMVs compared to parent bacteria. Proteins from the flagellum dominated. OMVs activated the pattern recognition receptors TLR2/4/5 as well as NOD1 and NOD2. EcO83-OMVs induced the production of pro- and anti-inflammatory cytokines in splenocytes and BMDCs. Intranasal administration of EcO83-OMVs inhibited airway hyperresponsiveness, and decreased airway eosinophilia, Th2 cytokine production and mucus secretion.

Conclusions
We demonstrate for the first time that intranasally administered OMVs from probiotic G- bacteria have an anti-allergic effect. Our study highlights the advantages of OMVs as a safe platform for the prophylactic treatment of allergy.

Graphical Abstract
Peroxiredoxin II regulates exosome secretion from dermal mesenchymal stem cells through the ISGylation signaling pathway
Authors: Han Ying-Hao , Mao Ying-Ying , Lee Kyung Ho , Cho Hee Jun , Yu Nan-Nan , Xing Xiao-Ya , Wang Ai-Guo , Jin Mei-Hua , Hong Kwan Soo , Sun Hu-Nan , Kwon Taeho 
Published: October 2023

AbstractBackgroundExosomes are small extracellular vesicles that play important roles in intercellular communication and have potential therapeutic applications in regenerative medicine. Dermal mesenchymal stem cells (DMSCs) are a promising source of exosomes due to their regenerative and immunomodulatory properties. However, the molecular mechanisms regulating exosome secretion from DMSCs are not fully understood.ResultsIn this study, the role of peroxiredoxin II (Prx II) in regulating exosome secretion from DMSCs and the underlying molecular mechanisms were investigated. It was discovered that depletion of Prx II led to a significant reduction in exosome secretion from DMSCs and an increase in the number of intracellular multivesicular bodies (MVBs), which serve as precursors of exosomes. Mechanistically, Prx II regulates the ISGylation switch that controls MVB degradation and impairs exosome secretion. Specifically, Prx II depletion decreased JNK activity, reduced the expression of the transcription inhibitor Foxo1, and promoted miR-221 expression. Increased miR-221 expression inhibited the STAT signaling pathway, thus downregulating the expression of ISGylation-related genes involved in MVB degradation. Together, these results identify Prx II as a critical regulator of exosome secretion from DMSCs through the ISGylation signaling pathway.ConclusionsOur findings provide important insights into the molecular mechanisms regulating exosome secretion from DMSCs and highlight the critical role of Prx II in controlling the ISGylation switch that regulates DMSC-exosome secretion. This study has significant implications for developing new therapeutic strategies in regenerative medicine.
Sarcopenia and myosteatosis diagnostic tool for gastrointestinal cancer: creatinine to cystatin C ratio as evaluation marker
Authors: Liu Hao , Wang Junjie , Tan Shanjun , Zhang Zhige , Yan Mingyue , Han Jun , Sui Xiangyu , Yang Fan , Wu Guohao 
Published: October 2023

Abstract
Objective
This study aimed to develop a simplified diagnostic tool for assessing sarcopenia and myosteatosis in gastrointestinal cancer patients, focusing on the creatinine to cystatin C ratio (CCR) as an evaluation marker.

Methods
955 patients were split into training (n = 671) and validation (n = 284) cohorts. Using logistic regression, risk factors for sarcopenia and myosteatosis were identified. The predictive capacity of the developed model was examined. The association between CCR and muscle imaging parameters, along with its impact on clinical outcomes, was analyzed.

Results
No significant differences were observed in baseline traits between cohorts. CCR emerged as a significant risk factor for both sarcopenia and myosteatosis. Nomograms for diagnosing these conditions demonstrated strong predictive ability, with AUC values indicating high accuracy (sarcopenia AUC: 0.865–0.872; myosteatosis AUC: 0.848–0.849). The clinical utility of the nomograms was confirmed through decision curve analysis. CCR showed significant association with muscle imaging parameters and was a reliable indicator for assessing the risk of sarcopenia, myosteatosis, and cachexia. Moreover, CCR was able to differentiate between patient survival and disease progression rates.

Conclusion
A diagnostic tool for sarcopenia and myosteatosis in gastrointestinal cancer patients was developed, with CCR being a pivotal biomarker for disease diagnosis and prognosis prediction.

Graphical Abstract
Circulating prolactin level in Juvenile Systemic Lupus Erythematosus and its correlation with disease activity: a case control study
Authors: Soliman Hend Mehawed , Fahmy Balsam Sherif , Ali Moataz Gamal , Shafie Eman Shafik 
Published: October 2023

Abstract
Background
The linkage between prolactin (PRL) and systemic lupus erythematosus (SLE) is still vague. Determination of serum levels of prolactin to reveal its role in patients with SLE is the aim of the study.

Methods
This is a case-control study performed on 40 children with SLE and 40 age- and sex-matched controls. Cases were further subdivided according to disease activity into mild, moderate, and severe groups using the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score. Serum prolactin levels were assayed by ELISA (enzyme-linked immunosorbent assay).

Results
prolactin level was significantly higher in SLE patients (17.3 ± 6.6 µg/L) than in controls (13.5 ± 5.3 µg/L) (P value = 0.005). Although the prolactin level was highest in severe cases (19.3 ± 7.7 µg/L), followed by moderate cases (17.0 ± 5.3 µg/L), and lowest in mild cases (14.0 ± 6.2 µg/L), the variance between the 3 groups was not statistically significant (P value = 0.212). A significant positive correlation between prolactin level and SLEDAI score was detected (r = 0.368) (P value = 0.019). Hyperprolactinemia was found in 8 patients (20%) but not in controls; 4 out of 8 patients with hyperprolactinemia (50%) showed neurological manifestations compared to only 3 out of 32 patients with a normal prolactin level (9.4%) (P value = 0.007).

Conclusion
A relationship between serum prolactin levels and juvenile SLE disease was detected. Neurological manifestations were more prevalent among SLE patients with hyperprolactinemia.
Preventative behaviours and COVID-19 infection in a Canadian cohort of people living with HIV
Authors: Hammond Keely , Lee Terry , Vulesevic Branka , Singer Joel , Needham Judy , Burchell Ann N. , Samji Hasina , Walmsley Sharon , Hull Mark , Jenabian Mohammad-Ali , Routy Jean-Pierre , Margolese Shari , Mandarino Enrico , Anis Aslam H. , Cooper Curtis L. , Costiniuk Cecilia T. 
Published: October 2023

AbstractFew studies have examined preventative behaviour practices with respect to COVID-19 among people living with HIV (human immunodeficiency virus). Using a cross-sectional survey from a Canadian Institutes of Health Research Canadian HIV Trials Network study (CTN 328) of people living with HIV on vaccine immunogenicity, we examined the relationships between participant characteristics and behavioural practices intended to prevent COVID-19 infection. Participants living in four Canadian urban centers were enrolled between April 2021–January 2022, at which time they responded to a questionnaire on preventative behaviour practices. Questionnaire and clinical data were combined to explore relationships between preventive behaviours and (1) known COVID-19 infection pre-enrolment, (2) multimorbidity, (3) developing symptomatic COVID-19 infection, and (4) developing symptomatic COVID-19 infection during the Omicron wave. Among 375 participants, 49 had COVID-19 infection pre-enrolment and 88 post-enrolment. The proportion of participants reporting always engaging in preventative behaviours included 87% masking, 79% physical distancing, 70% limiting social gatherings, 65% limiting contact with at-risk individuals, 33% self-isolating due to symptoms, and 26% self-quarantining after possible exposure. Participants with known COVID-19 infection pre-enrolment were more likely to self-quarantine after possible exposure although asymptomatic (65.0% vs 23.4%, p < 0.001; Chi-square test). Participants with multiple comorbidities more likely endorsed physical distancing (85.7% vs 75.5%, p = 0.044; Chi-square test), although this was not significant in logistic regression analysis adjusted for age, sex, race, number of household members, number of bedrooms/bathrooms in the household per person, influenza immunization, and working in close physical proximity to others. Overall, participants reported frequent practice of preventative behaviours.
ERRα promotes glycolytic metabolism and targets the NLRP3/caspase-1/GSDMD pathway to regulate pyroptosis in endometrial cancer
Authors: Su Pingping , Mao Xiaodan , Ma Jincheng , Huang Lixiang , Yu Lirui , Tang Shuting , Zhuang Mingzhi , Lu Zhonglei , Osafo Kelvin Stefan , Ren Yuan , Wang Xinrui , Lin Xite , Huang Leyi , Huang Xiaoli , Braicu Elena Ioana , Sehouli Jalid , Sun Pengming 
Published: October 2023

Abstract

Background
Tumor cells can resist chemotherapy-induced pyroptosis through glycolytic reprogramming. Estrogen-related receptor alpha (ERRα) is a central regulator of cellular energy metabolism associated with poor cancer prognosis. Herein, we refine the oncogenic role of ERRα in the pyroptosis pathway and glycolytic metabolism.

Methods
The interaction between ERRα and HIF-1α was verified using co-immunoprecipitation. The transcriptional binding sites of ERRα and NLRP3 were confirmed using dual-luciferase reporter assay and cleavage under targets and tagmentation (CUT&Tag). Flow cytometry, transmission electron microscopy, scanning electron microscopy, cell mito stress test, and extracellular acidification rate analysis were performed to investigate the effects of ERRα on the pyroptosis pathway and glycolytic metabolism. The results of these experiments were further confirmed in endometrial cancer (EC)-derived organoids and nude mice. In addition, the expression of ERRα-related pyroptosis genes was analyzed using The Cancer Genome Atlas and Gene Expression Omnibus database.

Results
Triggered by a hypoxic microenvironment, highly expressed ERRα could bind to the promoter of NLRP3 and inhibit caspase-1/GSDMD signaling, which reduced inflammasome activation and increased pyroptosis resistance, thereby resulting in the resistance of cancer cells to cisplatin. Moreover, ERRα activated glycolytic rate-limiting enzyme to bridge glycolytic metabolism and pyroptosis in EC. This phenomenon was further confirmed in EC-derived organoids and nude mice. CUT & Tag sequencing and The Cancer Genome Atlas database analysis showed that ERRα participated in glycolysis and programmed cell death, which resulted in EC progression.

Conclusions
ERRα inhibits pyroptosis in an NLRP3-dependent manner and induces glycolytic metabolism, resulting in cisplatin resistance in EC cells.