bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of intact protein and digested peptide techniques for high throughput proteotyping of ApoE
Authors: Maus Anthony , Figdore Dan , Milosevic Dragana , Algeciras-Schimnich Alicia , Bornhorst Joshua 
Published: November 2022

Abstract
Introduction
Apolipoprotein E (ApoE) genotyping has been shown to have diagnostic value in the evaluation of cardiovascular diseases and neurodegenerative disorders such as Alzheimer’s disease. Although genetic testing is well established for this application, liquid chromatography-mass spectrometry (LC–MS) has the potential to provide a high throughput, low-cost alternative for ApoE evaluation.

Methods
Serum samples were analyzed by peptide, intact protein, and genomic techniques. For peptide analysis, samples were digested with trypsin followed by liquid chromatography-tandem mass spectrometry analysis (LC–MS/MS) using a high-throughput multichannel LC system coupled to a Sciex 7500 mass spectrometer. For intact protein analysis, ApoE was immuno-purified using a monoclonal antibody immobilized on magnetic beads followed by high-resolution LC–MS analysis using an Exploris 480. DNA was extracted and evaluated using Sanger sequencing as a reference method.

Results and discussion
The peptide measurement method produced one discrepant result when compared to genomic sequencing (out of 38 sequenced samples), whereas the intact protein analysis followed by deconvolution resulted in two discrepant results and when the intact protein data was processed with chromatographic integration there were three discrepant results. Therefore, the intact protein method proved slightly less accurate, required longer analysis time, and is substantially more costly, while providing only a 30 min improvement in sample preparation time.

Conclusions
With current MS technology clinical laboratories appear to be better served to utilize trypsin digest sample preparation and LC–MS/MS as opposed to high-resolution LC–MS intact protein analysis techniques for evaluation of ApoE proteotype. Peptide analysis methods are capable of producing accurate results with high throughput and minimal cost.
Determination of temporal reproducibility and variability of cancer biomarkers in serum and EDTA plasma samples using a proximity extension assay
Authors: Christensen Troels D. , Maag Emil , Madsen Kasper , Lindgaard Sidsel Christy , Nielsen Dorte L. , Johansen Julia S. 
Published: November 2022

Abstract
Background
Proximity extension assay (PEA) is a novel antibody-based proteomic technology. Sparse data have been published concerning the matrix effect of serum vs. ethylenediamine tetraacetic acid (EDTA) plasma and the reproducibility of results obtained using PEA technology.

Methods
We analyzed samples with the PEA-based 92-plex Olink® immuno-oncology (I-O) assay. To estimate the matrix effect, we analyzed paired serum and EDTA plasma samples from 12 patients with biliary tract cancer. To evaluate the reproducibility, we used data from 7 studies, where 6–8 serum samples from patients with pancreatic cancer were used as bridging samples on 3 versions of the panel over a 2.5-years period.

Results
For the study of serum vs. plasma, 80 proteins were evaluable. The mean serum to EDTA plasma ratio ranged from 0.41–3.01. For 36 proteins, the serum and plasma values were not comparable due to high variability of the ratio, poor correlation, or possible concentration effect. For the bridging samples, the mean intra-study inter-assay coefficient of variation (CV) ranged from 11.3% to 26.1%. The mean inter-study CV was 42.0% before normalization and 26.2% after normalization. Inter-study results were well correlated (r ≥ 0.93), especially for studies using the same version of the panel (r ≥ 0.99).

Conclusion
For 44 of 92 proteins included in the Olink® I-O panel, the variation between results obtained using serum and EDTA plasma was constant and results were well correlated. Furthermore, samples could be stored for several years and used on different versions of the same PEA panel without it effecting results.
Hiring in border regions: experimental and qualitative evidence from a recruiter survey in Luxembourg
Authors: Gutfleisch Tamara , Samuel Robin 
Published: November 2022

AbstractFirms in border regions typically deal with heterogeneous applicant pools that include both (foreign) domestic workers and cross-border commuters. However, we know little about recruiters’ workforce needs and hiring practices in cross-border labour markets. Based on a survey of real recruiters in Luxembourg, this study presents experimental and qualitative findings on the role of country of residence in recruiters’ hiring intentions against foreigners. Luxembourg presents a rarely studied but highly relevant case for hiring practices owing to a combination of a strong economy, strict labour market regulations, and a transnational workforce. Drawing on data from a factorial survey experiment, we found no discrimination against Portuguese and French applicants living in Luxembourg. Yet, (highly skilled) cross-border workers from France and Germany faced disadvantages regarding recruiters’ hiring intentions. However, differences in effect sizes between foreigners and cross-border workers were small and not statistically significant. When further asked about the potential challenges of recruiting in Luxembourg’s cross-border labour market, respondents expressed concerns about flexibility, poor social fit, and cultural differences in hiring foreign and cross-border employees. Overall, our study provides further points of reference for studies on hiring intentions in cross-border labour markets across Europe.
Chronic constriction injury-induced changes in circular RNA expression profiling of the dorsal root ganglion in a rat model of neuropathic pain
Authors: Xiong Wanxia , Wei Min , Zhang Li , Wang Jie , Liu Fan , Wang Zhiyao 
Published: November 2022

Abstract
Background
The pathogenesis of neuropathic pain (NP) has not been fully elucidated. Gene changes in dorsal root ganglia (DRG) may contribute to the development of NP. Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that form covalently closed loop structures and are crucial for genetic and epigenetic regulation. However, little is known about circRNA changes in DRG neurons after peripheral nerve injury.

Methods
A sciatic nerve chronic constriction injury (CCI) model was established to induce neuropathic pain. We performed genome-wide circRNA analysis of four paired dorsal root ganglion (DRG) samples (L4–L5) from CCI and negative control (NC) rats using next-generation sequencing technology. The differentially expressed circRNAs (DEcircRNAs) were identified by differential expression analysis, and the expression profile of circRNAs was validated by quantitative PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of DEcircRNAs.

Results
A total of 374 DEcircRNAs were identified between CCI and NC rats using circRNA high-throughput sequencing. Among them, 290 were upregulated and 84 were downregulated in the CCI group. The expression levels of nine DEcircRNAs were validated by qPCR. Functional annotation analysis showed that the DEcircRNAs were mainly enriched in pathways and functions, including ‘dopaminergic synapse,’ ‘renin secretion,’ ‘mitogen-activated protein kinase signaling pathway,’ and ‘neurogenesis.’ Competing endogenous RNA analysis showed that the top 50 circRNAs exhibited interactions with four pain-related microRNAs (miRNAs). Circ:chr2:33950934–33955969 was the largest node in the circRNA–miRNA interaction network.

Conclusions
Peripheral nerve injury-induced neuropathic pain led to changes in the comprehensive expression profile of circRNAs in the DRG of rats. DEcircRNAs may advance our understanding of the molecular mechanisms underlying neuropathic pain.
Novel insights on association and reactivity of Bispectral Index, frontal electromyogram, and autonomic responses in nociception-sedation monitoring of critical care patients
Authors: Stewart Juhani A. , Särkelä Mika O. K. , Wennervirta Johanna , Vakkuri Anne P. 
Published: November 2022

Abstract
Background
Assessing nociception and sedation in mechanically ventilated patients in the ICU is challenging, with few reliable methods available for continuous monitoring. Measurable cardiovascular and neurophysiological signals, such as frontal EEG, frontal EMG, heart rate, and blood pressure, have potential in sedation and nociception monitoring. The hypothesis of this explorative study is that derived variables from the aforementioned signals predict the level of sedation, as described by the Richmond Agitation-Sedation score (RASS), and respond to painful stimuli during critical care.

Methods
Thirty adult postoperative ICU patients on mechanical ventilation and receiving intravenous sedation, excluding patients with primary neurological disorders, head injury, or need for continuous neuromuscular blockage. Bispectral Index (BIS), EMG power (EMG), EMG-derived Responsiveness Index (RI), and averaged blood pressure variability (ARV) were tested against RASS measurements. The aforementioned variables together with blood pressure and Surgical Pleth Index (SPI) were explored before and after painful stimuli (for example bronchoscopy, or pleural puncture) at varying RASS levels, to test variable responsiveness.

Results
BIS, EMG, and RI predicted RASS levels with a prediction probability (PK) of 0.776 for BIS, 0.761 for EMG, and 0.763 for RI. In addition, BIS, EMG, and ARV demonstrated responsiveness to painful stimuli during deep sedation (RASS score ≤ -3).

Conclusion
Variables derived from EEG and EMG are associated with sedation levels, as described by the RASS score. Furthermore, these variables, along with ARV, react with consistency to painful stimuli during deep sedation (RASS -5 to -3), offering novel tools for nociception-sedation monitoring of mechanically ventilated ICU patients requiring deep sedation.
A randomised controlled trial of acceptance and commitment therapy plus usual care compared to usual care alone for improving psychological health in people with motor neuron disease (COMMEND): study protocol
Authors: Gould Rebecca L. , Thompson Benjamin J. , Rawlinson Charlotte , Kumar Pavithra , White David , Serfaty Marc A. , Graham Christopher D. , McCracken Lance M. , Bursnall Matt , Bradburn Mike , Young Tracey , Howard Robert J. , Al-Chalabi Ammar , Goldstein Laura H. , Lawrence Vanessa , Cooper Cindy , Shaw Pamela J. , McDermott Christopher J. 
Published: November 2022

AbstractBackgroundMotor neuron disease (MND) is a rapidly progressive, fatal neurodegenerative disease that predominantly affects motor neurons from the motor cortex to the spinal cord and causes progressive wasting and weakening of bulbar, limb, abdominal and thoracic muscles. Prognosis is poor and median survival is 2–3 years following symptom onset. Psychological distress is relatively common in people living with MND. However, formal psychotherapy is not routinely part of standard care within MND Care Centres/clinics in the UK, and clear evidence-based guidance on improving the psychological health of people living with MND is lacking. Previous research suggests that Acceptance and Commitment Therapy (ACT) may be particularly suitable for people living with MND and may help improve their psychological health.AimsTo assess the clinical and cost-effectiveness of ACT modified for MND plus usual multidisciplinary care (UC) in comparison to UC alone for improving psychological health in people living with MND.MethodsThe COMMEND trial is a multi-centre, assessor-blind, parallel, two-arm RCT with a 10-month internal pilot phase. 188 individuals aged ≥ 18 years with a diagnosis of definite, laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis, and additionally the progressive muscular atrophy and primary lateral sclerosis variants, will be recruited from approximately 14 UK-based MND Care Centres/clinics and via self-referral. Participants will be randomly allocated to receive up to eight 1:1 sessions of ACT plus UC or UC alone by an online randomisation system. Participants will complete outcome measures at baseline and at 6- and 9-months post-randomisation. The primary outcome will be quality of life at six months. Secondary outcomes will include depression, anxiety, psychological flexibility, health-related quality of life, adverse events, ALS functioning, survival at nine months, satisfaction with therapy, resource use and quality-adjusted life years. Primary analyses will be by intention to treat and data will be analysed using multi-level modelling.DiscussionThis trial will provide definitive evidence on the clinical and cost-effectiveness of ACT plus UC in comparison to UC alone for improving psychological health in people living with MND.Trial registrationISRCTN Registry, ISRCTN12655391. Registered 17 July 2017,https://www.isrctn.com/ISRCTN12655391.Protocol version: 3.1 (10/06/2020).
The combination of arterial lactate level with GCS-pupils score to evaluate short term prognosis in traumatic brain injury: a retrospective study
Authors: Wang Yu-Mei , Zhu Ning , Zhou Yi-Min , Su Rui , Li Hong-Liang , Zhou Jian-Xin 
Published: November 2022

Abstract
Background
The aim of the study was to determine whether the combination of Glasgow Coma Scale (GCS) and Pupil responses score (GCSP) with arterial lactate level would be an index to predict the short term prognosis in patients with traumatic brain injury (TBI).

Methods
A retrospective study was performed enrolling all TBI patients admitted to intensive care unit (ICU) from 2019 to 2020. The demographics, clinical characteristics, and arterial lactate concentration were recorded. The GCSP and arterial blood analysis (ABG) with lactate was tested as soon as the patient was admitted to ICU. The Glasgow Outcome Scale (GOS) after discharge was regarded as the clinical outcome. A new index named GCSP-L was the combination of GCSP and lactate concentration. GCSP-L was the GCSP score (range 1-15) plus the lactate score (range 0-2). The lactate score was defined based on different lactate concentrations. If lactate was below 2 mmol/L, lactate score was 0, which above 5 mmol/L was 2 and between 2 and 5 mmol/L, the score was 1. As the range of GCSP was 1-15, the range of the GCSP-L was 1 to 17. The area under receiver operating characteristic curve (AUC) was calculated to evaluate the predictive ability of GCSP, lactate and GCSP-L. Statistical significance was set when p value < 0.05.

Results
A total of 192 TBI patients were included in the study. Based on GCSP, mild, moderate, and severe TBI were 13.02, 14.06 and 72.92%, respectively. There were 103 (53.65%) patients with the lactate concentration below 2 mmol/L (1.23 ± 0.37 mmol/l), 63 (32.81%) of the range from 2 to 5 (3.04 ± 2.43 mmol/l) and 26 (13.54%) were above 5 mmol/l (7.70 ± 2.43 mmol/l). The AUC was 0.866 (95% CI 0.827-0.904) for GCSP-L, 0.812 (95% CI 0.765-0.858) for GCSP and 0.629 (95% CI 0.570—0.0.688) for lactate. The AUC of GCSP-L was higher than the other two, GCSP and lactate alone.

Conclusions
The combination of GCSP and lactate concentration can be used to predict the short term prognosis in TBI patients.
Magnitude of husbands’ involvement in skilled birth attendant service utilization in Deder town, Oromiya, Ethiopia
Authors: Mohammed Abdusamed , Kifle Gizaw , Beshir Furo , Mume Abas , Abdullahi Yasin , Abdulwehab Remzia 
Published: November 2022

Abstract
Background
Husbands’ involvement strategies are employed to support their wives to access care, address the influence of gender inequality on maternal and newborn health, and promote husbands’ positive involvement as fathers. Yet, evidence of the husbands’ involvement in skilled birth attendant service utilization in Ethiopia is scarce, which limits the facility to improve institutional delivery services. Therefore, this study aimed to assess the magnitude of husbands’ involvement in skilled birth attendant service utilization among fathers of children of less than one year in Deder town, Oromiya, Ethiopia.

Methods
A community-based cross-sectional study was conducted using a structured questionnaire among 399 fathers selected by a simple random sampling technique. Data were collected through face-to-face interview from March 24 to April 20, 2021. Data entry was done by Epi-data version-4.2 and analyzed with SPSS version-21. Descriptive statistics used frequency, mean and median and presented by tables and figures. The level of significance was set at p-value ≤0.05 for multivariable logistic regression and an adjusted odds ratio with a 95% confidence interval was used to measure the degree of statistical significance of dependent and independent variables.

Result
The prevalence of husbands’ involvement in skilled birth attendant service utilization was 84.2%. The age group of 25 to 29 years (AOR = 2.63, CI: 1.124–6.142), prior knowledge of skilled-delivery attendants (AOR = 2.75, CI: 1.456–5.205) and good attitude towards skilled birth attendants (AOR =2.46, CI: 1.227–4.948) were statistically significant determinants of husbands’ involvement in skilled birth attendants service utilization.

Conclusion and recommendation
This study revealed that the husbands’ involvement in skilled birth attendants was high. Age, level of knowledge and attitude were the significant determinants of husbands’ involvement in promoting skilled-delivery attendants. Therefore, improving husbands’ level of knowledge and attitude towards skilled birth attendants is needed.
A single center analysis of first-line treatment in advanced KRAS mutant non-small cell lung cancer: real-world practice
Authors: Liu Yanxia , Gao Yuan , Wang Ying , Zhao Cong , Zhang Zhiyun , Li Baolan , Zhang Tongmei 
Published: November 2022

Abstract
Purpose
For the first-line treatment of KRAS mutant non-small cell lung cancer (NSCLC) patients, immunotherapy or platinum-based chemotherapy are the main treatment method. Here, we investigated the clinical efficacy and prognosis those two regimens as first-line treatment in real-world practice.

Methods
KRAS mutant NSCLC patients received chemotherapy or immunotherapy as first-line treatment from September 2014 to March 2022 were enrolled. Clinical characteristics, treatment scheme, clinical curative effect and follow-up data of enrolled patients were collected for analysis.

Results
Fifty patients received immunotherapy and 115 patients received chemotherapy were enrolled. Patients who received immunotherapy (HR = 0.350, 95%CI 0.156–0.781, P = 0.010), or pemetrexed-based regimen (HR = 0.486, 95%CI 0.255–0.928, P = 0.029), or antiangiogenic therapy (HR = 0.355, 95%CI 0.159–0.790, P = 0.011) were at a low risk of disease progression. And patients received antiangiogenic therapy had lower risk of death than those not (HR = 0.333, 95%CI 0.120–0.926, P = 0.035). Subgroup analysis revealed the immunotherapy compared to chemotherapy alone had lower risk of disease progression (HR = 0.377, 95%CI 0.166–0.856, P = 0.020) in PD-L1 expression ≥1% subgroup. And in non-G12C KRAS subgroup, but not in G12C KRAS subgroup, patients who received antiangiogenic therapy had lower risk of disease progression (HR = 0.254, 95%CI 0.098–0.656, P = 0.005) and death than those not (HR = 0.197, 95%CI 0.056–0.692, P = 0.011). In terms of different chemotherapy regimen, platinum-paclitaxel combined with antiangiogenic therapy achieved the highest ORR and DCR (P < 0.05), while the platinum-pemetrexed combined with antiangiogenic therapy had the longest PFS and OS (P < 0.001).

Conclusion
For the first-line treatment of KRAS mutant NSCLC patients, immunotherapy, antiangiogenic therapy, and pemetrexed-based regimen could obtain more benefits. Subgroup analysis revealed the benefits of immunotherapy compared to chemotherapy were applicable in PD-L1 expression≥1% subgroup, and antiangiogenic therapy could benefit non-G12C KRAS subgroup, but not G12C KRAS subgroup. In terms of different chemotherapy regimen, platinum-pemetrexed combined with antiangiogenic therapy may be the preferred chemotherapy regimen.
Attitudes of European students towards family decision-making and the harmonisation of consent systems in deceased organ donation: a cross-national survey
Authors: Molina-Pérez Alberto , Werner-Felmayer Gabriele , Van Assche Kristof , Jensen Anja M. B. , Delgado Janet , Flatscher-Thöni Magdalena , Hannikainen Ivar R. , Rodriguez-Arias David , Schicktanz Silke , Wöhlke Sabine 
Published: November 2022

Abstract
Background
European countries are increasingly harmonising their organ donation and transplantation policies. Although a growing number of nations are moving to presumed consent to deceased organ donation, no attempts have been made to harmonise policies on individual consent and the role of the family in the decision-making process. Little is known about public awareness of and attitudes towards the role of the family in their own country and European harmonisation on these health policy dimensions. To improve understanding of these issues, we examined what university students think about the role of the family in decision-making in deceased organ donation and about harmonising consent policies within Europe.

Methods
Using LimeSurvey© software, we conducted a comparative cross-sectional international survey of 2193 university students of health sciences and humanities/social sciences from Austria (339), Belgium (439), Denmark (230), Germany (424), Greece (159), Romania (190), Slovenia (190), and Spain (222).

Results
Participants from opt-in countries may have a better awareness of the family’s legal role than those from opt-out countries. Most respondents opposed the family veto, but they were more ambivalent towards the role of the family as a surrogate decision-maker. The majority of participants were satisfied with the family’s legal role. However, those who were unsatisfied preferred to limit family involvement. Overall, participants were opposed to the idea of national sovereignty over consent policies. They favoured an opt-out policy harmonisation and were divided over opt-in. Their views on harmonisation of family involvement were consistent with their personal preferences.

Conclusions
There is overall division on whether families should have a surrogate role, and substantial opposition to granting them sole authority over decision-making. If European countries were to harmonise their policies on consent for organ donation, an opt-out system that grants families a surrogate decision-making role may enjoy the widest public support.