bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing nitrous oxide cracking technology in the labour ward to reduce occupational exposure and environmental emissions: a quality improvement study*
Authors: Pinder A. , Fang L. , Fieldhouse A. , Goddard A. , Lovett R. , Khan‐Perez J. , Maclennan K. , Mason E. , MacCarrick T. , Shelton C. 
Published: September 2022

SummaryNitrous oxide, a potent greenhouse gas, is a common labour analgesic. One method which may reduce its carbon footprint is to ‘crack’ the exhaled gas into nitrogen and oxygen using catalytic destruction. In this quality improvement project, based on environmental monitoring and staff feedback, we assessed the impact of nitrous oxide cracking technology in the maternity setting. Mean ambient nitrous oxide levels were recorded during the final 30 minutes of uncomplicated labour in 36 cases and plotted on a run chart. Interventions were implemented in four stages, comprising: stage 1, baseline (12 cases); stage 2, cracking with nitrous oxide delivered and scavenged via a mouthpiece (eight cases); stage 3, cracking with nitrous oxide via a facemask with an air‐filled cushion (eight cases); stage 4, cracking with nitrous oxide via a low‐profile facemask, and enhanced coaching on the use of the technology (eight cases). The median ambient nitrous oxide levels were 71% lower than baseline in stage 2 and 81% lower in stage 4. Staff feedback was generally positive, though some found the technology to be cumbersome; successful implementation relies on effective staff engagement. Our results indicate that cracking technology can reduce ambient nitrous oxide levels in the obstetric setting, with potential for reductions in environmental impacts and occupational exposure.
Prevalence of pre‐operative anaemia in surgical patients: a retrospective, observational, multicentre study in Germany
Authors: Judd L. , Hof L. , Beladdale L. , Friederich P. , Thoma J. , Wittmann M. , Zacharowski K. , Meybohm P. , Choorapoikayil S. ,   the prevalence of pre‐operative anaemia in surgical patients (PANDORA) study collaborators
Published: September 2022

SummaryAnaemia is a risk factor for several adverse postoperative outcomes. Detailed data about the prevalence of anaemia are not available over a long time‐period in Germany. In this retrospective, observational, multicentre study, patients undergoing surgery in March in 2007, 2012, 2015, 2017 and 2019 were studied. The primary objective was the prevalence of anaemia at hospital admission. The secondary objectives were the association between anaemia and the number of units of red blood cells transfused, length of hospital stay and in‐hospital mortality. A total of 23,836 patients were included from eight centres. The prevalence of pre‐operative anaemia in patients aged ≥ 18 years decreased slightly from 37% in 2007 to 32.5% in 2019 (p = 0.01) and increased in patients aged ≤ 18 years from 18.8% in 2007 to 26.4% in 2019 (p > 0.001). The total amount of blood administered per 1000 patients decreased from 671.2 units in 2007 to 289.0 units in 2019. Transfusion rates in anaemic patients declined from 33.8% in 2007 to 19.1% in 2019 (p < 0.001) and in non‐anaemic patients from 8.4% in 2007 to 3.4% in 2019 (p < 0.001). Overall, the mortality rate remained constant over the years: 2.9% in 2007, 2.1% in 2012, 2.5% in 2015, 1.9% in 2017 and 2.5% in 2019. In the presence of anaemia, mortality was significantly increased compared with patients without anaemia (OR 5.27 (95%CI 4.13–6.77); p < 0.001). Red blood cell transfusion was associated with an increased risk of mortality (OR 14.98 (95%CI 11.83–19.03); p < 0.001). Using multivariable linear regression analysis with fixed effects, we found that pre‐operative anaemia (OR 2.08 (95%CI 1.42–3.05); p < 0.001) and red blood cell transfusion (OR 4.29 (95%CI 3.09–5.94); p < 0.001) were predictors of mortality but not length of stay (0.99 (95%CI 0.98–1.00) days; p = 0.12) and analysed years (2007 vs. 2019: OR 1.49 (95%CI 0.86–2.69); p = 0.07). Pre‐operative anaemia affects more than 30% of surgical patients in Germany and multidisciplinary action is urgently required to reduce adverse outcomes.
Toxicity signals associated with secukinumab: A pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database
Authors: Zheng Yi , Guo Xiaojing , Chen Chenxin , Chi Lijie , Guo Zhijian , Liang Jizhou , Wei Lianhui , Chen Xiao , Ye Xiaofei , He Jia 
Published: September 2022

AimsSecukinumab, the first interleukin 17A inhibitor, is widely used to treat immune diseases, including plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. Recently, many studies have reported adverse events associated with secukinumab, including gastrointestinal disorders, infections and infestations, and hypersensitive and nervous system disorders.ObjectiveHere, we aimed to explore the clinical characteristics, outcomes and time to onset of the four main toxicities of secukinumab using post‐marketing data.MethodsOur study utilized data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2015 to 2021, using disproportionality analysis. Toxicities were defined based on the standardized Medical Dictionary for Regulatory Activities queries. Two disproportionality methods were used to detect potential signals: information component (IC) and reporting odds ratio (ROR). The signals were defined as ROR025 > 1 and IC025 > 0.ResultsA total of 73 945 398 records were included in this study, of which 300 665 records were related to secukinumab. Diarrhoea (N = 3538), nasopharyngitis (N = 3458), pruritus (N = 4277) and rash (N = 3270) were the most common adverse events. Inflammatory bowel disease (IC025/ROR025 = 3.25/9.69), genital candidiasis (IC025/ROR025 = 3.46/11.54), dermatitis psoriasiform (IC025/ROR025 = 1.94/4.04) and anosmia (IC025/ROR025 = 1.62/3.17) had the highest IC025 values of all toxicities. The time to onset of the four toxicities was mainly concentrated in the first month. Some patients simultaneously presented with two or more toxicities.ConclusionThis pharmacovigilance study systematically explored the four main toxicities of secukinumab and provided new safety signals based on past safety information. Some high‐risk signals need to be given attention.
Fingolimod ameliorates schizophrenia‐like cognitive impairments induced by phencyclidine in male rats
Authors: Yu Xueli , Qi Xueyu , Wei Long , Zhao Liansheng , Deng Wei , Guo Wanjun , Wang Qiang , Ma Xiaohong , Hu Xun , Ni Peiyan , Li Tao 
Published: September 2022

Background and PurposeImprovement of cognitive deficits in schizophrenia remains an unmet need owing to the lack of new therapies and drugs. Recent studies have reported that fingolimod, an immunomodulatory drug for treating multiple sclerosis, demonstrates anti‐inflammatory and neuroprotective effects in several neurological disease models. This suggests its usefulness for ameliorating cognitive dysfunction in schizophrenia. Herein, we assessed the efficacy profile and mechanism of fingolimod in a rat model of phencyclidine (PCP)‐induced schizophrenia.Experimental ApproachMale Sprague–Dawley rats were treated with PCP for 14 days. The therapeutic effect of fingolimod on cognitive function was assessed using the Morris water maze and fear conditioning tests. Hippocampal neurogenesis and the expression of astrocytes and microglia were evaluated using immunostaining. Cytokine expression was quantified using multiplexed flow cytometry. Brain‐derived neurotrophic factor expression and phosphorylation of extracellular signal‐regulated kinase were determined using western blot analysis.Key ResultsFingolimod attenuated cognitive deficits and restored hippocampal neurogenesis in a dose‐dependent manner in PCP‐treated rats. Fingolimod treatment exerted anti‐inflammatory effects by inhibiting microglial activation and IL‐6 and IL‐1β pro‐inflammatory cytokine expression. The underlying mechanism involves the upregulation of brain‐derived neurotrophic factor protein expression and activation of the ERK signalling pathway.Conclusion and ImplicationsThis is the first preclinical assessment of the effects of fingolimod on cognitive function in a model for schizophrenia. Our results suggest the immune system plays an crucial role in cognitive alterations in schizophrenia and highlight the potential of immunomodulatory strategies to improve cognitive deficits in schizophrenia.
Circadian orchestration of host and gut microbiota in infection
Authors: Xia Yaoyao , Ding Xuezhi , Wang Shengyi , Ren Wenkai 
Published: September 2022

ABSTRACTCircadian rhythms are present in almost every organism and regulate multiple aspects of biological and physiological processes (e.g. metabolism, immune responses, and microbial exposure). There exists a bidirectional circadian interaction between the host and its gut microbiota, and potential circadian orchestration of both host and gut microbiota in response to invading pathogens. In this review, we summarize what is known about these intestinal microbial oscillations and the relationships between host circadian clocks and various infectious agents (bacteria, fungi, parasites, and viruses), and discuss how host circadian clocks prime the immune system to fight pathogen infections as well as the direct effects of circadian clocks on viral activity (e.g. SARS‐CoV‐2 entry and replication). Finally, we consider strategies employed to realign normal circadian rhythmicity for host health, such as chronotherapy, dietary intervention, good sleep hygiene, and gut microbiota‐targeted therapy. We propose that targeting circadian rhythmicity may provide therapeutic opportunities for the treatment of infectious diseases.
AIM2 upregulation promotes metastatic progression and PD‐L1 expression in lung adenocarcinoma
Authors: Zheng Jing‐Quan , Lin Che‐Hsuan , Lee Hsun‐Hua , Chang Wei‐Ming , Li Li‐Jie , Su Chia‐Yi , Lee Kang‐Yun , Chiu Hui‐Wen , Lin Yuan‐Feng 
Published: September 2022

AbstractCancer metastasis leading to the dysfunction of invaded organs is the main cause of the reduced survival rates in lung cancer patients. However, the molecular mechanism for lung cancer metastasis remains unclear. Recently, the increased activity of inflammasome appeared to correlate with the metastatic progression and immunosuppressive ability of various cancer types. Our results showed that the mRNA levels of absence in melanoma 2 (AIM2), one of the inflammasome members, are extensively upregulated in primary tumors compared with normal tissues derived from the TCGA lung adenocarcinoma (LUAD) database. Moreover, Kaplan‐Meier analysis demonstrated that a higher mRNA level of AIM2 refers to a poor prognosis in LUAD patients. Particularly, AIM2 upregulation is closely correlated with smoking history and the absence of EGFR/KRAS/ALK mutations in LUAD. We further showed that the endogenous mRNA levels of AIM2 are causally associated with the metastatic potentials of the tested LUAD cell lines. AIM2 knockdown suppressed but overexpression promoted the migration ability and lung colony–forming ability of tested LUAD cells. In addition, we found that AIM2 upregulation is closely associated with an increased level of immune checkpoint gene set, as well as programmed cell death‐ligand 1 (PD‐L1) transcript, in TCGA LUAD samples. AIM2 knockdown predominantly repressed but overexpression enhanced PD‐L1 expression via altering the activity of PD‐L1 transcriptional regulators NF‐κB/STAT1 in LUAD cells. Our results not only provide a possible mechanism underlying the AIM2‐promoted metastatic progression and immune evasion of LUAD but also offer a new strategy for combating metastatic/immunosuppressive LUAD via targeting AIM2 activity.
Hypoxia‐induced CXC chemokine ligand 14 expression drives protumorigenic effects through activation of insulin‐like growth factor‐1 receptor signaling in glioblastoma
Authors: Wei Sung‐Tai , Chiang Jung‐Ying , Wang Hwai‐Lee , Lei Fu‐Ju , Huang Yen‐Chih , Wang Chi‐Chung , Cho Der‐Yang , Hsieh Chia‐Hung 
Published: September 2022

AbstractHypoxic tumor microenvironment (HTM) promotes a more aggressive and malignant state in glioblastoma. However, little is known about the role and mechanism of CXC chemokine ligand 14 (CXCL14) in HTM‐mediated glioblastoma progression. In this study, we report that CXCL14 expression correlated with poor outcomes, tumor grade, and hypoxia‐inducible factor (HIF) expression in patients with glioblastoma. CXCL14 was upregulated in tumor cells within the hypoxic areas of glioblastoma. Hypoxia induced HIF‐dependent expression of CXCL14, which promoted glioblastoma tumorigenicity and invasiveness in vitro and in vivo. Moreover, CXCL14 gain‐of‐function in glioblastoma cells activated insulin‐like growth factor‐1 receptor (IGF‐1R) signal transduction to regulate the growth, invasiveness, and neurosphere formation of glioblastoma. Finally, systemic delivery of CXCL14 siRNA nanoparticles (NPs) with polysorbate 80 coating significantly suppressed tumor growth in vivo and extended the survival time in patient‐derived glioblastoma xenografts. Together, these findings suggest that HIF‐dependent CXCL14 expression contributes to HTM‐promoted glioblastoma tumorigenicity and invasiveness through activation of the IGF‐1R signaling pathway. CXCL14 siRNA NPs as an oligonucleotide drug can inhibit glioblastoma progression and constitute a translational path for the clinical treatment of glioblastoma patients.
The ATEAM study: Advances in technology to enhance PrEP adherence monitoring (ATEAM) among young men who have sex with men
Authors: Brothers Jennifer , Hosek Sybil , Keckler Kody , Anderson Peter L. , Xiong Di , Liu Honghu , Huhn Gregory 
Published: September 2022

AbstractYoung age has consistently correlated with lower adherence to pre‐exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Digital medicine, a dynamic healthcare platform of wearable physiological sensors and mobile communication technology that can respond to medication nonadherence rapidly, has the potential in promoting PrEP adherence. We evaluated the feasibility and acceptability of Proteus Discover, a digital monitoring adherence system, to measure PrEP adherence and provide real‐time feedback among cisgender YMSM and transgender women. One hundred HIV‐negative young men and transgender women ages 16–24 years were enrolled in a 24‐week randomized controlled crossover study to tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) coencapsulated with Proteus Discover versus TDF/FTC standard‐of‐care. Participants in the 12‐week Proteus Discover arm received weekly SMS text messages to promote pill taking based on Proteus Discover adherence data. Dried blood spots (DBS) were collected at 4‐week intervals for tenofovir diphosphate (TFV‐DP) in red blood cells as the referent and questionnaires were completed to assess acceptability, usability, and patterns of use. Linear mixed models analyzed the relationship between 30‐day adherence measured by DBS and Proteus Discover. PrEP adherence was high overall. Adherence, as measured by DBS, was correlated with adherence as measured by Proteus Discover (p value = 0.03). Most participants reported that Proteus Discover helped them take their PrEP daily and that the system was easy to use. However, a majority (53.5%–60.5%) disagreed with the statement that wearing the patch was not an issue. There was an incremental increase in TFV‐DP in DBS with adherence by Proteus Discover. More research is warranted to explore optimizing PrEP adherence for youth through real‐time monitoring.
Online SMART Recovery mutual support groups: Characteristics and experience of adults seeking treatment for methamphetamine compared to those seeking treatment for other addictive behaviours
Authors: Beck Alison K. , Larance Briony , Manning Victoria , Hides Leanne , Baker Amanda L. , Deane Frank P. , Shakeshaft Anthony , Raftery Dayle , Kelly Peter J. 
Published: September 2022

AbstractIntroductionThe COVID‐19 pandemic prompted the transition of Australian Self‐Management and Recovery Training (SMART) Recovery mutual support groups to virtual delivery. This study examined the self‐reported experience of online SMART Recovery groups for people seeking support for methamphetamine use (alone or in combination with other behaviours) compared to those who did not endorse methamphetamine use as a reason for seeking support.MethodsAn online survey invitation was embedded in the post‐group exit page. Items assessed participant demographic characteristics, experience, engagement and perceived contribution of the online group to recovery. Unique responses (n = 1414) were analysed using chi‐square.ResultsAfter alcohol, methamphetamine use was the second most common behaviour to prompt online SMART Recovery group attendance (n = 205, 14.5%). People attending for methamphetamine use were more likely to endorse multiple addictive behaviours (n = 137, 66.8% vs. n = 371, 30.7%, p < 0.001). Irrespective of whether people attended for methamphetamine use or not, participant ratings of experience, engagement and perceived contribution to recovery were positive and largely comparable. People attending for methamphetamine use were significantly less likely to set a 7‐day plan (72.7% vs. 81.9%; χ2 = 9.47, p = 0.002).Discussion and ConclusionsFindings support the acceptability of online SMART Recovery groups for people experiencing addictive behaviours, including methamphetamine use. To maximise the benefits of these groups, further evidence on how best to support people to develop a change plan within a time‐limited, online group setting is needed. Online mutual support groups may help to reach and support people who might not otherwise engage in treatment and support, including people who use methamphetamine.
Preterm postnatal complications and risk of attention‐deficit/hyperactivity disorder
Authors: Tso Winnie Wan‐Yee , Ho Frederick Ka Wing , Coghill David , Lee Tatia Mei‐Chun , Wang Yuliang , Lee So‐Lun , Wong Mabel Siu‐Chun , Yam Jason Cheuk Sing , Wong Ian Chi Kei , Ip Patrick 
Published: September 2022

AbstractAimTo investigate the association between the risk of attention‐deficit/hyperactivity disorder (ADHD) and preterm birth and determine how postnatal complications in children born preterm is associated with the risk of ADHD.MethodThis population‐based cohort study used data from the Hong Kong electronic medical records. We followed 359 614 children (48% female; 6–17 years old, mean 11 years 7 months, SD 3 years 2 months) born in public hospitals in Hong Kong from 1st January 2004 to 31st December 2014 and collected medical records and demographic details for mothers and children until 11th November 2020.ResultsThe risk of ADHD was 4.0% in children born at term and 5.1% in children born preterm. The odds ratio for ADHD was 2.08 (95% confidence interval [CI] 1.64–2.64) for children born extremely preterm, 1.64 (95% CI 1.46–1.85) for children born very preterm, and 1.15 (95% CI 1.08–1.23) for children born late preterm. Among preterm postnatal complications, only early respiratory disease, retinopathy of prematurity (ROP), and intraventricular haemorrhage were significant predictors of ADHD after controlling for preterm birth, other risk factors, and sociodemographic variables. The excess risk of ADHD among children born very preterm or late preterm could be partly explained by respiratory disease. ROP partially mediated the risk of ADHD in children born very preterm.InterpretationChildren born preterm in all subcategories, from extremely preterm to late preterm, have increased risk of ADHD. Early respiratory infection partially mediates the risk of ADHD in children born preterm.
Rationale and design of the phase 3a development programme (ONWARDS 1–6 trials) investigating once‐weekly insulin icodec in diabetes
Authors: Philis‐Tsimikas Athena , Bajaj Harpreet S. , Begtrup Kamilla , Cailleteau Roman , Gowda Amoolya , Lingvay Ildiko , Mathieu Chantal , Russell‐Jones David , Rosenstock Julio 
Published: September 2022

AbstractAimTo describe the phase 3a ONWARDS clinical development programme investigating insulin icodec (icodec), a once‐weekly basal insulin, including the design and rationale for each of the ONWARDS 1–6 trials.Materials and MethodsSix randomized controlled trials have been initiated in adults with type 2 diabetes (T2D) (insulin‐naive: ONWARDS 1, 3 and 5; previously insulin‐treated: ONWARDS 2 and 4) and type 1 diabetes (T1D) (ONWARDS 6). Each trial will investigate icodec use in a unique clinical scenario, with consideration of long‐term safety and varied comparator treatments (insulin glargine U100 or U300 or insulin degludec). ONWARDS 5 will incorporate real‐world elements and a digital dose titration solution to guide icodec dosing. The primary objective for each of the trials is to compare the change in HbA1c from baseline to week 26 or week 52 between icodec and comparator arms. Secondary objectives include investigating other glycaemic control and safety parameters, such as fasting glucose, time in glycaemic range and hypoglycaemia. Patient‐reported outcomes will assess treatment satisfaction.ConclusionsThe ONWARDS 1–6 trials will evaluate the efficacy and safety of once‐weekly icodec compared with currently available daily basal insulin analogues in T2D and T1D. These trials will generate comprehensive evidence of icodec use in diverse populations across the spectrum of diabetes progression and treatment experience.
Innate immune sensing of nucleic acid in endodontic infection
Authors: Ji Xiao , Zhang Lan , Yang Fan , Huang Ding‐ming 
Published: September 2022

AbstractInnate immunity is the first line of defence and fights against microorganisms. Nucleic acids are important pathogen‐associated molecular patterns to be recognized in innate immunity. There are three types of nucleic acid sensors, including endosomal sensors (NA‐sensing TLRs), cytosolic DNA sensors (cGAS and AIM2) and cytosolic RNA sensors (RLG‐I, MDA5 and LGP2). Recent studies have shown that nucleic acid sensors are expressed differently in a variety of dental pulp cells and mediate inflammation through complex pathways. Nucleic acid sensing may play a vital role in the development of endodontic infection. This review aims to summarize and analyse the possible roles of various nucleic acid sensors in endodontic infection. It may help better understand the pathogenesis of these diseases and find new strategies for prevention and treatment.