bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of alcohol, tobacco, cannabis, and other substances during the first wave of the SARS-CoV-2 pandemic in Europe: a survey on 36,000 European substance users
Authors: Manthey Jakob , Kilian Carolin , Carr Sinclair , Bartak Miroslav , Bloomfield Kim , Braddick Fleur , Gual Antoni , Neufeld Maria , O’Donnell Amy , Petruzelka Benjamin , Rogalewicz Vladimir , Rossow Ingeborg , Schulte Bernd , Rehm Jürgen 
Published: April 2021

AbstractBackgroundSARS-CoV-2 reached Europe in early 2020 and disrupted the private and public life of its citizens, with potential implications for substance use. The objective of this study was to describe possible changes in substance use in the first months of the SARS-CoV-2 pandemic in Europe.MethodsData were obtained from a cross-sectional online survey of 36,538 adult substance users from 21 European countries conducted between April 24 and July 22 of 2020. Self-perceived changes in substance use were measured by asking respondents whether their use had decreased (slightly or substantially), increased (slightly or substantially), or not changed during the past month. The survey covered alcohol (frequency, quantity, and heavy episodic drinking occasions), tobacco, cannabis, and other illicit drug use. Sample weighted data were descriptively analysed and compared across substances.ResultsAcross all countries, use of all substances remained unchanged for around half of the respondents, while the remainder reported either a decrease or increase in their substance use. For alcohol use, overall, a larger proportion of respondents indicated a decrease than those reporting an increase. In contrast, more respondents reported increases in their tobacco and cannabis use during the previous month compared to those reporting decreased use. No distinct direction of change was reported for other substance use.ConclusionsOur findings suggest changes in use of alcohol, tobacco and cannabis during the initial months of the pandemic in several European countries. This study offers initial insights into changes in substance use. Other data sources, such as sales statistics, should be used to corroborate these preliminary findings.
Is fidelity to a complex behaviour change intervention associated with patient outcomes? Exploring the relationship between dietitian adherence and competence and the nutritional status of intervention patients in a successful stepped-wedge randomised clinical trial of eating as treatment (EAT)
Authors: Beck Alison K. , Baker Amanda L. , Carter Gregory , Robinson Laura , McCarter Kristen , Wratten Christopher , Bauer Judith , Wolfenden Luke , Britton Benjamin 
Published: April 2021

AbstractBackgroundBehavioural medicine is characterised by findings for the effectiveness and efficacy of complex behaviour change interventions. Comparatively, scant attention has been paid to key intervention components or mechanisms of action. Evaluating relationships between process variables (fidelity) and intervention effects is central to addressing this imbalance. Accordingly, in the current study, we sought to explore the magnitude and direction of effect between fidelity predictors (dietitian adherence and competence) and intervention effects (patient nutritional status) during the intervention phase of a real-world, stepped-wedge evaluation of ‘EAT: Eating As Treatment’.MethodsThe EAT clinical trial was conducted within five major Australian hospitals located in Queensland, Western Australia, Victoria and South Australia between 2013 and 2016. EAT is a dietitian-delivered health behaviour change intervention designed to reduce malnutrition in head and neck cancer (HNC) patients undergoing radiotherapy. Dietitian adherence and competence ratings were derived from a 20% random sample of audio-recorded dietetic consultations (n=194) conducted after dietitians (n=18) were trained in EAT. Sessions were coded by trained, independent, coders using a study checklist, the Behaviour Change Counselling Index (BECCI) and items from the Cognitive Therapy Scale-Revised (CTS-R). Patient nutritional status was measured using the Patient-Generated Subjective Global Assessment (PGSGA).ResultsDietitian adherence to a written nutrition plan (β=7.62, 95% CI=0.65 to 14.58,p=0.032), dietitian adherence to behaviour change counselling (β=0.69, 95% CI =0.02 to 1.38,p=0.045) and competence in delivering behaviour change counselling (β=3.50, 95% CI =0.47 to 6.53,p=0.024) were significant predictors of patient nutritional status. Dietitian adherence and competence ratings were higher during consultations with intervention patients at greater risk of malnutrition.ConclusionsThis study contributes new insights into the relationship between fidelity and treatment outcome by demonstrating that dietitian adherence and competence is greater when working with more challenging patients. This is likely central to the demonstrated success of the EAT intervention in reducing malnutrition and highlights the importance of ensuring that providers are adequately equipped to flexibly integrate intervention elements according to patient need.Trial registrationThis study is a process analysis of a stepped-wedge randomised controlled trial prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12613000320752; Date of registration 21/03/2013).
Curculigoside promotes osteogenic differentiation of ADSCs to prevent ovariectomized-induced osteoporosis
Authors: You Wei-Li , Xu Zheng-Long 
Published: April 2021

Abstract
Background
Curculigoside is a natural phenolic glycoside compound produced by Curculigo orchioides Gaertn. This study aimed to explore the effects of curculigoside in promoting the osteogenic differentiation of adipose-derived stem cells (ADSCs) as well as the underlying mechanism.

Methods
ADSCs were treated with curculigoside at different concentrations (0 μmol/L, 1 μmol/L, 2.5 μmol/L, 5 μmol/L, 10 μmol/L, and 20 μmol/L), and cell viability was assessed by CCK-8 assay. Then, the alkaline phosphatase (ALP) activity was determined, and alizarin red S (ARS) staining was performed to measure the extracellular mineralization of curculigoside. Information about protein-chemical interactions is provided by the search tool for interactions of chemicals (STITCH) database. Then, LY294002 was administered to explore the mechanism by which curculigoside promotes the osteogenic differentiation of ADSCs. Western blot assays were performed to assess changes in the expression of osteogenic-related markers and the phosphorylation of PI3K and AKT. Finally, we established an ovariectomized (OVX)-induced osteoporosis mouse model and administered curculigoside to explore the effects of curculigoside in preventing bone loss in vivo.

Results
The CCK-8 assay indicated that curculigoside did not induce cytotoxicity at a concentration of 5 μmol/L after 48 h. The ALP and ARS results revealed that the induced group had higher ALP activity and calcium deposition than the control group. Moreover, the curculigoside group exhibited increased biomineralization, ALP activity, and ARS staining compared to the induced and control groups, and these effects were partially inhibited by LY294002. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the target genes of curculigoside were mainly involved in the PI3K-Akt signaling pathway. PCR and western blot analysis showed that the expression of RUNX2, ALP, and Osterix was upregulated in curculigoside-treated ADSCs, but this effect was partially reversed by the PI3K inhibitor LY294002. Moreover, the curculigoside-treated group exhibited significantly increased phosphorylation of AKT to P-AKT compared with the osteogenic induction group. After treatment with curculigoside, the mice had a higher bone volume than the OVX mice, suggesting partial protection from cancellous bone loss. In addition, when LY294002 was added, the protective effects of curculigoside could be neutralized.

Conclusions
Curculigoside could induce the osteogenic differentiation of ADSCs and prevent bone loss in an OVX model through the PI3K/Akt signaling pathway.
One-stage posterior laminectomy with instrumented fusion and foraminotomy for cervical ossification of posterior longitudinal ligament with radiculopathy pain
Authors: Su Bao , Shen Jieliang , Luo Xiaoji , Quan Zhengxue , Jiang Dianming , Peng Xiaohua , Tang Ke 
Published: April 2021

Abstract
Objective
To explore the clinical efficacy of posterior LFF for cervical OPLL with radicular pain of upper limbs

Methods
Between January 2014 and January 2018, 48 OPLL patients with radicular pain symptoms of upper limbs who underwent a one-stage posterior laminectomy and instrumented fusion with/without foraminotomy were reviewed retrospectively and divided into two groups: LF group (laminectomy with instrumented fusion without foraminotomy) and LFF group (laminectomy with instrumented fusion and foraminotomy). Clinical data were assessed and compared between the two groups. The radicular pain of upper limbs and neck was measured using the visual analog scale (VAS). The neurological function was evaluated with the American Spinal Injury Association (ASIA) scale. Changes of sagittal alignment were investigated by postoperative plain x-ray or computed tomography (CT). Moreover, the decompression of the spinal cord was evaluated based on postoperative MRI.

Results
All the 48 patients were followed up for 24–42 months with an average follow-up time of 31.1±5.3 months. A total of 56 cervical intervertebral foramens were enlarged in 48 patients, including 40 cases (83.3%) with 1 intervertebral foramen enlargement and 8 cases (16.7%) with 2 intervertebral foramen enlargements. There were no significant differences in intraoperative blood loss, postoperative drainage amount, Japanese Orthopaedic Association (JOA) scores, JOA recovery rates, VAS scores for neck pain, and ASIA grade between two groups. The mean operative time was shorter in the LF group compared with the LFF group. The VAS score for arm pain was significantly lower while the surgical duration was longer in group B. No statistical difference was observed between the two groups in terms of C2–C7 SVA, cervical lordosis, focal angulation at the foraminotomy segment, and local spinal cord angle. Compared with the LF group, there was no segmental kyphosis or instability where the additional posterior foraminotomy was performed in the LFF group.

Conclusions
One-stage posterior LFF can achieve satisfied clinical efficacy in improving neurological function and relieving the radicular pain of the upper limbs for OPLL patients with radiculopathy symptoms.
Risk factors of postoperative delirium after cardiac surgery: a meta-analysis
Authors: Chen Haiyan , Mo Liang , Hu Hongjuan , Ou Yulan , Luo Juan 
Published: April 2021

Abstract
Background
Postoperative delirium is a frequent event after cardiac surgery. This meta-analysis aimed to identify relevant risk factors.

Method
In this meta-analysis, all original researches regarding patients undergoing mixed types of cardiac surgery (excluding transcatheter procedures) and postoperative delirium were evaluated for inclusion. On July 28th 2020, we searched PubMed, Embase, Web of Science and Scopus. Data about name of first author, year of publication, inclusion and exclusion criteria, research design, setting, method of delirium assessment, incidence of delirium, odds ratio (OR) and corresponding 95% confidence interval (CI) of risk factors, and other information relevant was collected. OR and 95% CI were used as metrics for summarized results. Random effects model was applied.

Results
Fourteen reports were included with a total sample size of 13,286. The incidence of delirium ranged from 4.1 to 54.9%. Eight risk factors were identified including aging, diabetes, preoperative depression, mild cognitive impairment, carotid artery stenosis, NYHA functional class III or IV, time of mechanical ventilation and length of intensive care unit stay.

Conclusion
In this study several risk factors associated with postoperative delirium after cardiac surgery were identified. Utilizing the information may allow us to identifying patients at high risk of developing postoperative delirium prior to delirium onset.
Current status of ctDNA in precision oncology for hepatocellular carcinoma
Authors: Li Yan , Zheng Yuanyuan , Wu Liwei , Li Jingjing , Ji Jie , Yu Qiang , Dai Weiqi , Feng Jiao , Wu Jianye , Guo Chuanyong 
Published: April 2021

AbstractThe conventional method used to obtain a tumor biopsy for hepatocellular carcinoma (HCC) is invasive and does not evaluate dynamic cancer progression or assess tumor heterogeneity. It is thus imperative to create a novel non-invasive diagnostic technique for improvement in cancer screening, diagnosis, treatment selection, response assessment, and predicting prognosis for HCC. Circulating tumor DNA (ctDNA) is a non-invasive liquid biopsy method that reveals cancer-specific genetic and epigenetic aberrations. Owing to the development of technology in next-generation sequencing and PCR-based assays, the detection and quantification of ctDNA have greatly improved. In this publication, we provide an overview of current technologies used to detect ctDNA, the ctDNA markers utilized, and recent advances regarding the multiple clinical applications in the field of precision medicine for HCC.
Childhood stunting and associated factors among irrigation and non-irrigation user northwest, Ethiopia: a comparative cross-sectional study
Authors: Sema Balew , Azage Muluken , Tirfie Mulat 
Published: April 2021

Abstract
Background
Stunting is a critical public health problem of developing countries like Ethiopia. Different interventions like irrigation activity have been carried out by the government of Ethiopia to improve the nutritional status of the community. However, there is scanty of data on childhood stunting and its associated factors between irrigation user and non-irrigation user.

Objective
To assess the magnitude of childhood stunting and its associated factors between irrigation and non-irrigation user in North Mecha District, Northwest Ethiopia.

Methods
A community-based comparative cross-sectional study design was employed from October to November 2019. A systematic sampling was used to draw mothers with children age 6–59 months (582 irrigated and 582 non- irrigated household users). Data were collected using questionnaire and anthropometric measurement tools. Multivariable logistic regression was used to identify the predictors of stunting. Adjusted odds ratios with 95% CI were used to determine the degree of association between independent and outcome variable. A-p-value < 0.05 was used as cutoff point to declare statistically significant variables with the outcome variable.

Results
The prevalence of childhood stunting (6–59 months) among irrigation users [32.8% at 95%CI [29.1%-36.7%]] was slightly lower than non-users [40.2% at 95%CI [[36.3%-44.2%]]]. However, the difference did not show significant variation. The odds of childhood stunting were higher among a child from a mother had no antenatal visit, a child whose age was between 12 and 47 months, a child from a mother who did not use water and soap always for washing hands, and a child who had fever.

Conclusion
The prevalence of childhood stunting was high and did not show significant variation between irrigation and non-irrigation users. A child from mother had no antenatal visit, whose age was between 12 and 47 months, a mother who did not use water and soap always for washing hands, and who had fever were factors associated with higher child stunting. Thus, the identified modifiable factors should be strengthened to reduce stunting.
Implications of cardiac markers in risk-stratification and management for COVID-19 patients
Authors: Li Pengping , Wu Wei , Zhang Tingting , Wang Ziyu , Li Jie , Zhu Mengyan , Liang Yuan , You Wenhua , Li Kening , Ding Rong , Huang Bin , Wu Lingxiang , Duan Weiwei , Han Yi , Li Xuesong , Tang Xin , Wang Xin , Shen Han , Wang Qianghu , Yan Hong , Xia Xinyi , Ji Yong , Chen Hongshan 
Published: April 2021

Abstract
Background
COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients.

Methods
A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression.

Results
Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50–68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4–4.8]).

Conclusions
COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.
Clinical effects of breast milk enema on meconium evacuation in premature infants: study protocol for a randomized controlled trial
Authors: Zheng Liqiang , Gai Li , Gao Jinyue , Kong Chaonan , Wang Yali , Sun Fangli , Liu Sitong , Yu Xinying , Yang Fan , Jiang Hong 
Published: April 2021

Abstract
Background
Delayed meconium evacuation is an important cause of intestinal dysfunction in preterm infants. There are many methods to induce defecation in preterm infants: however, the effects are controversial. Finding a new intervention method to promote meconium evacuation in premature infants is necessary. Therefore, in the proposed study, the effectiveness of breast milk enema on complete meconium evacuation and time to achieve full enteral feeding will be investigated in preterm infants.

Methods/design
The study is a randomized, open-label, parallel-group, and single-center clinical trial. A total of 294 preterm infants will be recruited and stratified based on gestational age. Then, the infants will be assigned in a randomized block design to the intervention and control groups with a 1:1 ratio. Preterm infants in the control and intervention groups will receive saline enema and breast milk enema, respectively. The primary outcomes will be the time to achieve complete meconium evacuation from birth and time to achieve full enteral feeding from birth in preterm infants. The secondary outcomes will include hospitalization days, body weight at discharge, duration of total parenteral nutrition, cholestasis, and adverse events.

Discussion
The results of this trial will determine whether breast milk enema shortens the time to complete meconium evacuation and the time to achieve full enteral feeding in extremely preterm and preterm infants. Furthermore, the study results may provide a new, safe, inexpensive, and easy-to-use intervention to effectively evacuate meconium in preterm infants.

Trial registration
ISRCTN Registry ISRCTN17847514. Registered on September 14, 2019
Synthesis of oxadiazole-2-oxide derivatives as potential drug candidates for schistosomiasis targeting SjTGR
Authors: Li Gongming , Guo Qingqing , Feng Chao , Chen Huan , Zhao Wenjiao , Li Shu , Hong Yang , Sun Dequn 
Published: April 2021

Abstract
Background
Schistosomiasis is a chronic parasitic disease that affects millions of people’s health worldwide. Because of the increasing drug resistance to praziquantel (PZQ), which is the primary drug for schistosomiasis, developing new drugs to treat schistosomiasis is crucial. Oxadiazole-2-oxides have been identified as potential anti-schistosomiasis reagents targeting thioredoxin glutathione reductase (TGR).

Methods
In this work, one of the oxadiazole-2-oxides derivatives furoxan was used as the lead compound to exploit a series of novel furoxan derivatives for studying inhibitory activity against both recombinant Schistosoma japonicum TGR containing selenium (rSjTGR-Sec) and soluble worm antigen protein (SWAP) containing wild-type Schistosoma japonicum TGR (wtSjTGR), in order to develop a new leading compound for schistosomiasis. Thirty-nine novel derivatives were prepared to test their activity toward both enzymes. The docking method was used to detect the binding site between the active molecule and SjTGR. The structure–activity relationship (SAR) of these novel furoxan derivatives was preliminarily analyzed.

Results
It was found that several new derivatives, including compounds 6a–6d, 9ab, 9bd and 9be, demonstrated greater activity toward rSjTGR-Sec or SWAP containing wtSjTGR than did furoxan. Interestingly, all intermediates bearing hydroxy (6a–6d) showed excellent inhibitory activity against both enzymes. In particular, compound 6d with trifluoromethyl on a pyridine ring was found to have much higher inhibition toward both rSjTGR-Sec (half-maximal inhibitory concentration, IC50,7.5nM) and SWAP containing wtSjTGR (IC50 55.8nM) than furoxan. Additionally, the docking method identified the possible matching sites between 6d and Schistosoma japonicum TGR (SjTGR), which theoretically lends support to the inhibitory activity of 6d.

Conclusion
The data obtained herein showed that 6d with trifluoromethyl on a pyridine ring could be a valuable leading compound for further study.

Graphical Abstract