bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world comparative effectiveness of three single-inhaler dual bronchodilators for the treatment of COPD
Authors: Li Jiaying , Dell'Aniello Sophie , Ernst Pierre , Suissa Samy 
Published: June 2023

BackgroundSingle-inhaler dual bronchodilators are now recommended as initial treatment of COPD for patients with multiple exacerbations or with moderate or severe dyspnoea. It is unclear whether there are differences in effectiveness among commonly used dual bronchodilators.MethodsWe identified a cohort of COPD patients, aged ≥40 years, treated during 2017–2020, from the UK Clinical Practice Research Datalink, a real-world practice setting. Inhaled corticosteroid-naïve patients initiating vilanterol–umeclidinium (VIL–UME) were compared with those initiating olodaterol–tiotropium (OLO–TIO) or indacaterol–glycopyrronium (IND–GLY) dual bronchodilators primarily on the incidence of moderate and severe COPD exacerbation over 1 year, and corresponding hazard ratios (HRs), after adjustment by propensity score weighting.ResultsThe cohort included 15 224 initiators of VIL–UME, 5536 initiators of OLO–TIO and 5059 initiators of IND–GLY. The HR of a moderate or severe exacerbation with VIL–UME was 0.91 (95% CI 0.85–0.97) compared with OLO–TIO and 0.96 (95% CI 0.89–1.03) compared with IND–GLY. The risk of severe exacerbation was not different for VIL–UME when compared with OLO–TIO (HR 1.04, 95% CI 0.86–1.26) and IND–GLY (HR 1.05, 95% CI 0.86–1.28). All-cause mortality was lower with VIL–UME compared with IND–GLY (HR 0.82, 95% CI 0.68–0.98), but not compared with OLO–TIO (HR 0.87, 95% CI 0.72–1.04).ConclusionIn a real-world setting of COPD treatment, the three dual bronchodilator combinations were similarly effective on the risk of a severe exacerbation of COPD. However, the VIL–UME and IND–GLY combinations may confer slightly superior effectiveness than OLO–TIO on the risk of moderate or severe exacerbation. The potential lower mortality with VIL–UME warrants further investigation.
Decreased expression of H19/miR-675 ameliorates muscle atrophy by regulating the IGF1R/Akt/FoxO signaling pathway
Authors: Zhang He , Wang Fei , Pang Xiangsheng , Zhou Yue , Li Shiming , Li Wenjiong , Zhang Peng , Chen Xiaoping 
Published: June 2023

Abstract
Background
Long non-coding RNA (lncRNA) H19 is one of the most highly expressed and conserved transcripts in mammalian development, and its functions have been fully discussed in many contexts including tumorigenesis and skeletal muscle development. However, its exact role in muscle atrophy remains largely unknown. This study investigated the effect of lncRNA H19 on muscle atrophy and the potential underlying mechanism.

Methods
Hindlimb suspension (HS) of C57BL/6 mice and starvation of C2C12 cells with PBS were conducted to induce atrophy. Real-time PCR and Western blotting were used to measure the expression of RNAs and proteins. LncRNA H19 and its encoded miR-675 were overexpressed or inhibited in different models of muscle atrophy. Immunofluorescence was carried out to examine the cross-sectional area (CSA) and minimal Feret’s diameter (MFD) of myofibers and myotube diameter.

Results
The expression levels of lncRNA H19 and miR-675 were significantly reduced in both the soleus and gastrocnemius muscles in response to HS. Overexpression of lncRNA H19 led to an increase in Atrogin-1 mRNA expression, and this effect was reversed by inhibiting miR-675. The overexpression of miR-675 aggravated both HS- and starving-induced muscle atrophy by inhibiting the IGF1R/Akt signaling pathway and promoting FoxO/Atrogin-1 expression. Conversely, miR-675 inhibition had the opposite effects.

Conclusion
The lncRNA H19/miR-675 axis can induce muscle atrophy, and its downregulation in mice with HS-induced muscle atrophy may act as a protective mechanism against this condition.
Methodological considerations on real-world evidence studies of monoclonal antibodies against the CGRP-pathway for migraine: a systematic review
Authors: Vandenbussche Nicolas , Pisarek Karolina , Paemeleire Koen 
Published: June 2023

Abstract
Background
Real-world data are accumulating on the effectiveness, tolerability and safety of anti-calcitonin gene-related peptide pathway monoclonal antibodies for the preventive treatment of migraine. We performed a systematic review of the methodology of prospective, observational, clinic-based real-world evidence studies with these drugs in both episodic and chronic migraine.

Methods
The objectives were to evaluate the definitions and reported outcomes used, and to perform a risk of bias assessment for each of the different studies. PubMed and EMBASE were systematically queried for relevant scientific articles. Study quality assessment of the included studies was conducted using the “National Heart, Lung and Blood Institute (NHLBI) Study Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group”.

Results
Forty-six studies fitted the criteria for the systematic review and were included in the analysis. Ten studies (21.7%) defined a migraine day for the study, while only 5 studies defined a headache day for the study (10.9%). The most common primary endpoint/objective of the studies was change in monthly migraine days (n = 16, 34.8%), followed by responder rate (n = 15, 32.6%) and change in monthly headache days (n = 5, 10.9%). Eight studies (17.4%) did not define the primary endpoint/objective. Thirty-three studies were graded as “good” quality and 13 studies were graded as “fair”.

Conclusion
Our analysis shows rather significant heterogeneity and/or lack of predefined primary outcomes/objectives, definitions of outcomes measures and the use of longitudinal monitoring (e.g. headache diaries). Standardization of terminology, definitions and protocol procedures for real-world evidence studies of preventive treatments for migraine are recommended.

Trial registration
This study was registered with PROSPERO with ID CRD42022369366.
Genome-wide identification and characterization of Glutathione S-Transferases (GSTs) and their expression profile under abiotic stresses in tobacco (Nicotiana tabacum L.)
Authors: Mo Zejun , Huang Ying , Pu Tianxiunan , Duan Lili , Pi Kai , Luo Jiajun , Long Benshan , Lu Anbin , Liu Renxiang 
Published: June 2023

Abstract
Background
Glutathione S-transferases (GSTs) are large and multifunctional proteases that play an important role in detoxification, protection against biotic and abiotic stresses, and secondary metabolite transportation which is essential for plant growth and development. However, there is limited research on the identification and function of NtGSTs.

Results
This study uses K326 and other six tobacco varieties (Hongda, HG, GDH11, Va116, VG, and GDH88) as materials to conduct comprehensive genome-wide identification and functional characterization of the GST gene in tobacco. A total of 59 NtGSTs were identified and classified into seven subfamilies via the whole-genome sequence analysis, with the Tau type serving as the major subfamily. The NtGSTs in the same branch of the evolutionary tree had similar exon/intron structure and motif constitution. There were more than 42 collinear blocks between tobacco and pepper, tomato, and potato, indicating high homology conservation between them. Twelve segmental duplicated gene pairs and one tandem duplication may have had a substantial impact on the evolution and expansion of the tobacco GST gene family. The RT-qPCR results showed that the expression patterns of NtGSTs varied significantly among tissues, varieties, and multiple abiotic stresses, suggesting that NtGST genes may widely respond to various abiotic stresses and hormones in tobacco, including NtGSTF4, NtGSTL1, NtGSTZ1, and NtGSTU40.

Conclusions
This study provides a comprehensive analysis of the NtGST gene family, including structures and functions. Many NtGSTs play a critical regulatory role in tobacco growth and development, and responses to abiotic stresses. These findings offer novel and valuable insights for understanding the biological function of NtGSTs and the reference materials for cultivating highly resistant varieties and enhancing the yield and quality of crops.
The effect of LED light quality on the carotenoid metabolism and related gene expression in the genus Brassica
Authors: Frede Katja , Winkelmann Sara , Busse Linda , Baldermann Susanne 
Published: June 2023

Abstract
Background
New vegetable production systems, such as vertical farming, but also well-established in-door production methods led to the implementation of light emitting diodes (LEDs). LEDs are the most important light sources in modern indoor-production systems and offer the possibility for enhancing growth and specific metabolites in planta. Even though the number of studies investigating the effects of LED lighting on vegetable quality has increased, the knowledge about genus variability is limited. In the present study, the effect of different LED spectra on the metabolic and transcriptional level of the carotenoid metabolism in five different Brassica sprouts was investigated. Cruciferous vegetables are one of the main food crops worldwide. Pak choi (Brassica rapa ssp. chinensis), cauliflower (Brassica oleracea var. botrytis), Chinese cabbage (Brassica rapa ssp. pekinensis), green kale (Brassica oleracea ssp. sabellica) and turnip cabbage (Brassica oleracea spp. gongylodes) sprouts were grown under a combination of blue & white LEDs, red & white LEDs or only white LEDs to elucidate the genus-specific carotenoid metabolism.

Results
Genus-specific changes in plant weight and on the photosynthetic pigment levels as well as transcript levels have been detected. Interestingly, the transcript levels of the three investigated carotenoid biosynthesis genes phytoene synthase (PSY), β-cyclase (βLCY) and β-carotene hydroxylase (βOHASE1) were increased under the combination of blue & white LEDs in the majority of the Brassica sprouts. However, only in pak choi, the combination of blue & white LEDs enhanced the carotenoid levels by 14% in comparison to only white LEDs and by ~ 19% in comparison to red & white LEDs.

Conclusions
The effects of light quality differ within a genus which leads to the conclusion that production strategies have to be developed for individual species and cultivars to fully benefit from LED technology.
Heparin-resistance in AL amyloidosis: a case report
Authors: van Ede Elisabeth S. , Hoeks Marlijn P. A. , Hofland Jan , Linssen Vera D. , van Kuppevelt Toin H. , Versteeg Elly M. , Hafmans Theo G. , Diepstra Arjan , Kusters Benno , Vermorgen Sanne M. M. 
Published: June 2023

AbstractBackgroundNon-AT-III mediated heparin-resistance during CPB occurs by complex-forming with heparin-binding proteins. Currently, there are no specific recommendations for non-AT-III mediated heparin-resistance.Case presentationWe present a fatal case of a 70-yr-old male-patient undergoing cardiac-surgery in which refractory heparin-resistance was observed. The massive AL amyloidosis found at autopsy is thought to be responsible and illustrates that awareness and knowledge of the etiology and perioperative strategies of non-AT-III mediated heparin-resistance is important.ConclusionFor anticoagulation during cardiopulmonary bypass surgery in case of a non-AT-III medicated heparin resistance, we refer to the decision tree added to this manuscript and if necessary to consider direct thrombin inhibitors, such as bivalirudin or argatroban, as it bypasses the complexing pathway.
On the Q statistic with constant weights in meta-analysis of binary outcomes
Authors: Kulinskaya Elena , Hoaglin David C. 
Published: June 2023

Abstract
Background
Cochran’s Q statistic is routinely used for testing heterogeneity in meta-analysis. Its expected value (under an incorrect null distribution) is part of several popular estimators of the between-study variance, $$\tau ^2$$

τ
2

. Those applications generally do not account for use of the studies’ estimated variances in the inverse-variance weights that define Q (more explicitly, $$Q_{IV}$$

Q

IV

). Importantly, those weights make approximating the distribution of $$Q_{IV}$$

Q

IV

rather complicated.

Methods
As an alternative, we are investigating a Q statistic, $$Q_F$$

Q
F

, whose constant weights use only the studies’ arm-level sample sizes. For log-odds-ratio (LOR), log-relative-risk (LRR), and risk difference (RD) as the measures of effect, we study, by simulation, approximations to distributions of $$Q_{IV}$$

Q

IV

and $$Q_F$$

Q
F

, as the basis for tests of heterogeneity.

Results
The results show that: for LOR and LRR, a two-moment gamma approximation to the distribution of $$Q_F$$

Q
F

works well for small sample sizes, and an approximation based on an algorithm of Farebrother is recommended for larger sample sizes. For RD, the Farebrother approximation works very well, even for small sample sizes. For $$Q_{IV}$$

Q

IV

, the standard chi-square approximation provides levels that are much too low for LOR and LRR and too high for RD. The Kulinskaya et al. (Res Synth Methods 2:254–70, 2011) approximation for RD and the Kulinskaya and Dollinger (BMC Med Res Methodol 15:49, 2015) approximation for LOR work well for $$n \ge 100$$

n
≥
100

but have some convergence issues for very small sample sizes combined with small probabilities.

Conclusions
The performance of the standard $$\chi ^2$$

χ
2

approximation is inadequate for all three binary effect measures. Instead, we recommend a test of heterogeneity based on $$Q_F$$

Q
F

and provide practical guidelines for choosing an appropriate test at the .05 level for all three effect measures.
Chronic kidney disease in primary care: risk of cardiovascular events, end stage kidney disease and death
Authors: Borg Rikke , Kriegbaum Margit , Grand Mia Klinten , Lind Bent , Andersen Christen Lykkegaard , Persson Frederik 
Published: June 2023

Abstract
Background
The prevalence of chronic kidney disease (CKD) is increasing globally. Early diagnosis in primary care may have a role in ensuring proper intervention. We aimed to determine the prevalence and outcome of CKD in primary care.

Methods
We performed an observational cohort study in primary care in Copenhagen (2001–2015). Outcomes were stroke, myocardial infarction (MI), heart failure (HF), peripheral artery disease (PAD), all-cause- and cardiovascular mortality. We combined individuals with normal kidney function and CKD stage 2 as reference. We conducted cause-specific Cox proportional regressions to calculate the hazard ratios for outcomes according to CKD group. We explored the associations between kidney function and the outcomes examined using eGFR as a continuous variable modelled with penalised splines. All models were adjusted for age, gender, diabetes, hypertension, existing CVD, heart failure, LDL cholesterol and use of antihypertensive treatment.

Results
We included 171,133 individuals with at least two eGFR measurements of which the majority (n = 157,002) had eGFR > 60 ml/min/1.73m2 at index date, and 0.05% were in CKD stage 5. Event rates were low in eGFR > 60 ml/min/1.73m2 but increased in those with higher stages of CKD. In adjusted analyses we observed an increase in hazard rates for every outcome with every increment in CKD stage. Compared to the reference group, individuals in CKD stage 4 had double the hazard rate of PAD, MI, cardiovascular and all-cause mortality.

Conclusions
Our data from a large primary care cohort demonstrate an early increase in the risk of adverse outcomes already at CKD stage 3. This underlines the importance of studying early intervention in primary care.
Serum cytokines in second trimester pregnancy and their relationship with spontaneous preterm births in the Ribeirão Preto and São Luiz cohorts
Authors: Turra Suzana Eggers , Damaso Ênio Luis , Veiga Eduardo Carvalho de Arruda , Cardoso Viviane Cunha , Bettiol Heloisa , Cavalli Ricardo Carvalho 
Published: June 2023

Abstract
Objective
To evaluate the association between second trimester plasma cytokine levels in asymptomatic pregnant women and preterm births (PTB) in an attempt to identify a possible predictor of preterm birth.

Methods
The study design was a nested case–control study including women with singleton a gestational age between 20–25(+ 6) weeks from two Brazilian cities. The patients were interviewed, Venous blood samples were collected. The participants were again evaluated at birth. A total of 197 women with PTB comprised the case group. The control group was selected among term births (426 patients). Forty-one cytokines were compared between groups.

Results
When only spontaneous PTB were analyzed, GRO, sCD40L and MCP-1 levels were lower in the case group (p < 0.05). Logarithmic transformation was performed for cytokines with discrepant results, which showed increased levels of IL-2 in the group of spontaneous PTB (p < 0.05). In both analyses, the incidence of maternal smoking and of a history of preterm delivery differed significantly between the case and control groups. In multivariate analysis, only serum GRO levels differed between the case and control groups.

Conclusion
Lower second trimester serum levels of GRO in asymptomatic women are associated with a larger number of PTB. This finding may reflect a deficient maternal inflammatory response.
Lost in translation? Information quality in pediatric pre-hospital medical emergencies with a language barrier in Germany
Authors: Müller Frank , Schröder Dominik , Schäning Jennifer , Schmid Sybille , Noack Eva Maria 
Published: June 2023

Abstract
Background
In pediatric medical emergencies, paramedics and emergency physicians must often rely on the information of third parties, often caregivers, to gather information. Failing to obtain relevant information may lead to misinterpretation of symptoms and subsequent errors in decision making and clinical treatment. Thus, children and/or caregivers with limited proficiency of the locally spoken language may be at risk for medical errors. This study analyzes logs of rescue missions to determine whether paramedics could obtain essential information from German-speaking and foreign-language children and their caregivers.

Methods
We conducted a secondary data analysis based on retrospective data on pediatric patients of four emergency medical services (EMS) stations in Northern Germany. We defined language discordance with communication difficulties as main exposure. We used documentation quality as outcome defined as existing information on (a) pre-existing conditions, (b) current medication, and (c) events prior to the medical emergency. Statistical analyses include descriptive statistics, simple regression and multivariable regression. As multivariable regression model, a logistic regression was applied with documentation quality as dependent variable and language discordance with communication difficulties as independent variable adjusted for age, sex and Glasgow Coma Scale (GCS).

Results
Data from 1,430 pediatric rescue missions were analyzed with 3.1% (n = 45) having a language discordance with communication difficulties. Patients in the pediatric foreign-language group were younger compared to German-speaking patients. Thorough documentation was more frequent in German-speaking patients than in patients in the foreign-language group. Pre-existing conditions and events prior to the medical emergency were considerably more often documented in German-speaking than for foreign-language patients. Documentation of medication did not differ between these groups. The adjustment of sex, age and GCS in the multivariable analysis did not change the results.

Conclusion
Language barriers are hindering paramedics to obtain relevant information in pediatric pre-hospital emergencies. This jeopardizes the safe provision of paramedic care to children who themselves or their caregivers are not fluent in German language. Further research should focus on feasible ways to overcome language barriers in pre-hospital emergencies.

Trial registration
This is a retrospective secondary data analysis of a study that was registered at the German Clinical Trials Register (No. DRKS00016719), 08/02/2019.
The relationship between depressive and anxious symptoms and school attendance among adolescents seeking psychological services in a public general hospital in China: a cross-sectional study
Authors: Zhao Guoqing , Wang Bin , Li Hui , Ren Honghong , Jiao Zhian 
Published: June 2023

Abstract
Background
School attendance problems (SAPs), whether absenteeism or dropout, are strongly associated with poor outcomes for adolescents. We examined multiple variables that influence SAPs to identify potential leverage points for improving school attendance.

Methods
Self-reported SAPs and demographic information was collected from 392 adolescents in adolescents presenting to the general hospital for psychological services. PHQ-9 and GAD-7 were applied to assess the severity of depressive and anxious symptoms. We constructed logistic regression analysis and the Chi-Square Automatic Interaction Detection (CHAID) segmentation analysis via SPSS Decision Tree to identifying risk factors for the development of SAPs in adolescents.

Results
SAPs were self-reported by 252 (64.3%) adolescents. The SAPs group and non-SAPs group showed a significant difference in age, PHQ9 total scores, GAD7 total scores, schools, siblings, residence, parental marital quality, general health, regular exercise, and regular diet. A post hoc comparison between the two groups showed that the frequency of SAPs was significantly higher in the moderately-severe and severe depressive groups compared with other three groups (none, mild, moderate). The frequency of SAPs in severe anxious groups was significantly different from the none-anxious group. According to the binary logistic regression analysis, the depressive severity, siblings, residence, marital quality of parents, general health, and regular diet were correlated with the SAPs among adolescents. The adjusted OR of SAPs according to moderately-severe depressive symptoms was 10.84 (95%CI: 1.967–59.742) and severe depressive symptoms was 6.659 (95%CI: 1.147–38.666). In the decision tree model, PHQ-9 severity was extracted as the first splitting variable, with regular exercise and residence as the second, and siblings as the third. The ROC curves for predicting SAPs showed a fair diagnostic accuracy of the model with AUCs of CHAID model (0.705,95%CI:0.652–0.759, P = 0.000) and logistic regression model (0.777,95%CI:0.729–0.824, P = 0.000).

Conclusion
Our study provides insights into the associations between depressive symptoms and poor school attendance and identifies a number of risk factors associated with SAPs. Effective intervention by mental health practitioners, more attention by policy makers, and further research in this area are urgently needed for adolescents.