bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practices of public procurement and the risk of corrupt behavior before and after the government transition in México
Authors: Falcón-Cortés Andrea , Aldana Andrés , Larralde Hernán 
Published: March 2022

AbstractCorruption has a significant impact on economic growth, democracy, and inequality. It has sever consequences at the human level. Public procurement, where public resources are used to purchase goods or services from the private sector, are particularly susceptible to corrupt practices. However, government turnover may bring significant changes in the way public contracting is done, and thus, in the levels and types of corruption involved in public procurement. In this respect, México lived a historical government transition in 2018, with the new government promising a crackdown on corruption. In this work, we analyze data from more than 1.5 million contracts corresponding from 2013 to 2020, to study to what extent this change of government affected the characteristics of public contracting, and we try to determine whether these changes affect how corruption takes place. To do this, we propose a statistical framework to compare the characteristics of the contracting practices within each administration, separating the contracts in different classes depending on whether or not they were made with companies that have now been identified as being involved in corrupt practices. We find that while the amount of resources spent with companies that turned out to be corrupt has decreased substantially, many of the patterns followed to contract these companies were maintained, and some of those in which changes did occur, are suggestive of a larger risk of corruption.
Understanding China’s urban system evolution from web search index data
Authors: Guo Hao , Zhang Weiyu , Du Haode , Kang Chaogui , Liu Yu 
Published: March 2022

AbstractThe spatial inequilibrium phenomenon is apparent during China’s rapid urbanization in the past four decades. As the fertility rate decreases and the population ages, this phenomenon will become more critical. To accurately forecast the future economic development of China, it is necessary to quantify the attractiveness of individual cities. This study introduces web search data to quantify the attractiveness of cities with a fine spatial scale (prefecture-level city) and relatively long-term span (nine years). Results confirm that the estimated city attractiveness can unravel a city’s capability to attract labor force, and suggest that tourism and health care functions of a city have a positive effect to the city’s attractiveness. Additionally, China’s north-south gap in economic development has been widened in the past decade, and 11 cities with nationwide influence have prosperous development potential. This study provides a new lens for predicting China’s economic development, as well as its spatial patterns.
On the Immersive Properties of High Dynamic Range Video
Authors: Hinde Stephen J. , Noland Katy C. , Thomas Graham A. , Bull David R. , Gilchrist Iain D. 
Published: March 2022

This paper presents the results from two studies which used a dual-task methodology to measure an audience's experience of immersion while watching video under typical television viewing conditions. Immersion was measured while participants watched either a high dynamic range, wide color gamut video or a standard dynamic range, standard color gamut video, in high definition or ultra-high definition. Other video parameters were carefully measured and controlled.
The study found that high dynamic range, wide color gamut video is significantly more immersive than standard dynamic range, standard color gamut video in the chosen configuration. However, there was no evidence of significant differences in immersion between high-definition and ultra-high-definition resolutions.
HSP90 Inhibition Overcomes Resistance to Molecular Targeted Therapy in BRAFV600E-mutant High-grade Glioma
Authors: Sasame Jo , Ikegaya Naoki , Kawazu Masahito , Natsumeda Manabu , Hayashi Takahiro , Isoda Masataka , Satomi Kaishi , Tomiyama Arata , Oshima Akito , Honma Hirokuni , Miyake Yohei , Takabayashi Katsuhiro , Nakamura Taishi , Ueno Toshihide , Matsushita Yuko , Iwashita Hiromichi , Kanemaru Yu , Murata Hidetoshi , Ryo Akihide , Terashima Keita , Yamanaka Shoji , Fujii Yukihiko , Mano Hiroyuki , Komori Takashi , Ichimura Koichi , Cahill Daniel P. , Wakimoto Hiroaki , Yamamoto Tetsuya , Tateishi Kensuke 
Published: March 2022

Abstract

Purpose:
Molecular targeted therapy using BRAF and/or MEK inhibitors has been applied to BRAFV600E-mutant high-grade gliomas (HGG); however, the therapeutic effect is limited by the emergence of drug resistance.

Experimental Design:
We established multiple paired BRAFV600E-mutant HGG patient-derived xenograft models based on tissues collected prior to and at relapse after molecular targeted therapy. Using these models, we dissected treatment-resistant mechanisms for molecular targeted therapy and explored therapeutic targets to overcome resistance in BRAFV600E HGG models in vitro and in vivo.

Results:
We found that, despite causing no major genetic and epigenetic changes, BRAF and/or MEK inhibitor treatment deregulated multiple negative feedback mechanisms, which led to the reactivation of the MAPK pathway through c-Raf and AKT signaling. This altered oncogenic signaling primarily mediated resistance to molecular targeted therapy in BRAFV600E-mutant HGG. To overcome this resistance mechanism, we performed a high-throughput drug screening to identify therapeutic agents that potently induce additive cytotoxicity with BRAF and MEK inhibitors. We discovered that HSP90 inhibition combined with BRAF/MEK inhibition coordinately deactivated the MAPK and AKT/mTOR pathways, and subsequently induced apoptosis via dephosphorylation of GSK3β (Ser9) and inhibition of Bcl-2 family proteins. This mediated potent cytotoxicity in vitro and in vivo in refractory models with acquired resistance to molecular targeted therapy.

Conclusions:
The combination of an HSP90 inhibitor with BRAF or MEK inhibitors can overcome the limitations of the current therapeutic strategies for BRAFV600E-mutant HGG.
Venetoclax Cooperates with Ionizing Radiation to Attenuate Diffuse Midline Glioma Tumor Growth
Authors: Madhavan Krishna , Balakrishnan Ilango , Lakshmanachetty Senthilnath , Pierce Angela , Sanford Bridget , Fosmire Susan , Elajaili Hanan B. , Walker Faye , Wang Dong , Nozik Eva S. , Mitra Siddhartha S. , Dahl Nathan A. , Vibhakar Rajeev , Venkataraman Sujatha 
Published: March 2022

AbstractPurpose:Tumor relapse after radiotherapy is a major hurdle in treating pediatric H3K27M-mutant diffuse midline gliomas (DMG). Radiotherapy-induced stress increases association of BCL2 family of proteins with BH3 pro-apoptotic activators preventing apoptosis. We hypothesized that inhibition of radiotherapy-induced BCL2 with a clinically relevant inhibitor, venetoclax, will block BCL2 activity leading to increased apoptosis. BCL2 has never been implicated in DMG as a radiotherapy-induced resistant mechanism.Experimental Design:We performed an integrated genomic analysis to determine genes responsible for radioresistance and a targeted drug screen to identify drugs that synergize with radiation in DMG. Effect of venetoclax on radiation-naïve and 6 Gy radiation on cells was evaluated by studying cell death, changes in BCL2 phosphorylation, reactive oxygen species (ROS), and apoptosis, as well as BCL2 association with BH3 apoptosis initiators. The efficacy of combining venetoclax with radiation was evaluated in vivo using orthotopic xenograft models.Results:BCL2 was identified as a key regulator of tumor growth after radiation in DMGs. Radiation sensitizes DMGs to venetoclax treatment independent of p53 status. Venetoclax as a monotherapy was not cytotoxic to DMG cells. Postradiation venetoclax treatment significantly increased cell death, reduced BCL2–BIM association, and augmented mitochondrial ROS leading to increased apoptosis. Combining venetoclax with radiotherapy significantly enhanced the survival of mice with DMG tumors.Conclusions:This study shows that venetoclax impedes the antiapoptotic function of radiation-induced BCL2 in DMG, leading to increased apoptosis. Results from these preclinical studies demonstrate the potential use of the BCL2 inhibitor venetoclax combined with radiotherapy for pediatric DMG.
Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1)
Authors: Neuman Rugina I. , Baars Milan D. , Saleh Langeza , Broekhuizen Michelle , Nieboer Daan , Cornette Jérôme , Schoenmakers Sam , Verhoeven Michel , Koch Birgit C.P. , Russcher Henk , van den Berg Sjoerd A.A. , van den Meiracker Anton H. , Visser Willy , Danser A.H. Jan 
Published: March 2022

Background:
Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors.

Methods:
Here, we examined whether the proton pump inhibitor omeprazole could acutely reduce sFlt-1 and ET-1 (measured as CT-proET-1 [C-terminal pro-endothelin-1]), or increase free PlGF (placental growth factor) in 20 women with confirmed preeclampsia. Primary outcome was specified as the difference in sFlt-1, PlGF, or CT-proET-1 after 4 days of omeprazole versus 20 preeclamptic women not receiving omeprazole.

Results:

Mean maternal age was 30 years, and median gestational age was 30
+3
weeks. Baseline sFlt-1 levels were identical in both groups, and the same was true for PlGF or CT-proET-1. After 4 days, sFlt-1 levels remained similar in women not receiving omeprazole compared with women receiving omeprazole, while the levels of PlGF and CT-proET-1 also did not differ between groups. Women receiving omeprazole had a similar prolongation of pregnancy after inclusion compared with those in the nonomeprazole group (median 15 versus 14 days). Except for a higher neonatal intubation rate in the nonomeprazole group (31% versus 4%,
P
=0.02), there were no differences in maternal/perinatal complications. Finally, making use of the placenta perfusion model, we established that both omeprazole and its S-isomer, esomeprazole, when maternally applied, reached the fetal compartment (fetal-to-maternal ratio’s 0.43–0.59), while only esomeprazole inhibited placental sFlt-1 release.

Conclusions:
Administration of omeprazole to women with confirmed preeclampsia does not alter their circulating levels of sFlt-1, PlGF, or ET-1, arguing against a role of this drug as a treatment for this syndrome.
Forgotten keyworkers: the experiences of British seafarers during the COVID-19 pandemic
Authors: Devereux Helen , Wadsworth Emma 
Published: March 2022

AbstractDuring the COVID-19 pandemic the UK Government designated seafarers as keyworkers. This article explores their experiences in an industry operating under international legislation designed to ensure and maintain their employment and working conditions. Three hundred and fifty-two British seafarers completed an online questionnaire. The findings revealed two key themes: the erosion of the terms and conditions of those who work at sea, and the differing experiences of those who were precariously employed on single voyage contracts in comparison to those in permanent employment. In contrast with precariously employed individuals, more seafarers with permanent contracts were joining the vessel as normal and fewer were not being paid having been unable to join a ship as scheduled. In a similar vein, fewer permanently employed seafarers were adversely financially impacted during the pandemic. The article concludes that those with the weakest employment relationships have experienced the greatest challenges as a result of the COVID-19 pandemic–a scenario which was possible as a result of the limited enforcement of the regulatory framework intended to protect those who work at sea.
Different Exercise Time on 5-HT and Anxiety-like Behavior in the Rat With Vascular Dementia
Authors: Fan Yongzhao , Zhang Linlin , Kong Xiaoyang , Liu Kun , Wu Hao 
Published: March 2022

Background Previous studies have demonstrated that pre-exercise suppresses anxiety-like behavior, but the effects of different exercise times on vascular dementia induced anxiety-like behavior have not been well investigated. Objective The present study aims to investigate the underlying neurochemical mechanism of different pre-vascular-dementia exercise times on 5-HT and anxiety-like behavior in rats with vascular dementia. Methods 32 Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham group (S group, n = 8), vascular dementia group (VD group, n = 8), 1-week physical exercise and vascular dementia group (1WVD group, n = 8), and 4 weeks physical exercise and vascular dementia group (4WVD group, n = 8). 1 week and 4 weeks of voluntary wheel running were used as pre-exercise training. The vascular dementia model was established by bilateral common carotid arteries occlusion (BCCAo) for 1 week. But bilateral common carotid arteries were not ligated in the sham group. The level of hippocampal 5-HT was detected with in vivo microdialysis coupled with high-performance liquid chromatography (MD-HPLC). Elevated plus maze (EPM), open field (OF), and light/dark box test were used to test anxiety-like behavior. Results Compared with the C group, the hippocampal 5-HT was significantly decreased in the VD group after 1 week of ligated operation. The hippocampal 5-HT levels in 1WVD and 4WVD groups were substantially higher than the level in the VD group. The hippocampal 5-HT level has no significant difference among C, 1WVD, and 4WVD. Behavioral data suggested that the rats in the VD group developed obvious anxiety-like behavior after 1 week of ligation surgery. Still, the rats in 1WVD and 4WVD groups did not show significant anxiety-like behavior. Conclusion Both 1 week and 4 weeks of voluntary running wheel exercise can inhibit the anxiety-like behavior in rats with vascular dementia by upregulating 5-HT levels in the hippocampus in the VD model.
Genomic architecture of 5S rDNA cluster and its variations within and between species
Authors: Ding Qiutao , Li Runsheng , Ren Xiaoliang , Chan Lu-yan , Ho Vincy W. S. , Xie Dongying , Ye Pohao , Zhao Zhongying 
Published: March 2022

Abstract
Background
Ribosomal DNAs (rDNAs) are arranged in purely tandem repeats, preventing them from being reliably assembled onto chromosomes during generation of genome assembly. The uncertainty of rDNA genomic structure presents a significant barrier for studying their function and evolution.

Results
Here we generate ultra-long Oxford Nanopore Technologies (ONT) and short NGS reads to delineate the architecture and variation of the 5S rDNA cluster in the different strains of C. elegans and C. briggsae. We classify the individual rDNA’s repeating units into 25 types based on the unique sequence variations in each unit of C. elegans (N2). We next perform assembly of the cluster by taking advantage of the long reads that carry these units, which led to an assembly of 5S rDNA cluster consisting of up to 167 consecutive 5S rDNA units in the N2 strain. The ordering and copy number of various rDNA units are consistent with the separation time between strains. Surprisingly, we observed a drastically reduced level of variation in the unit composition in the 5S rDNA cluster in the C. elegans CB4856 and C. briggsae AF16 strains than in the C. elegans N2 strain, suggesting that N2, a widely used reference strain, is likely to be defective in maintaining the 5S rDNA cluster stability compared with other wild isolates of C. elegans or C. briggsae.

Conclusions
The results demonstrate that Nanopore DNA sequencing reads are capable of generating assembly of highly repetitive sequences, and rDNA units are highly dynamic both within and between population(s) of the same species in terms of sequence and copy number. The detailed structure and variation of the 5S rDNA units within the rDNA cluster pave the way for functional and evolutionary studies.
Effect of age adjustment on two triage methods
Authors: Kemp Kirsi , Alakare Janne , Kätkä Minna , Lääperi Mitja , Lehtonen Lasse , Castrén Maaret 
Published: March 2022

Abstract
Background
Most emergency departments rely on acuity assessment, triage, to recognize critically ill patients that need urgent treatment, and to allocate resources according to need. The accuracy of commonly used triage instruments such as the Emergency Severity Index (ESI) is lower for older adults compared to young patients. We aim to examine, whether adjusting the triage category by age leads to improvement in sensitivity without excessive increase in patient numbers in the higher triage categories. The primary outcome measure was 3-day mortality and secondary outcomes were 30-day mortality, hospital admission, and HDU/ICU admissions.

Methods
We gathered data of all adult patients who had an unscheduled visit to any of our three emergency departments within one month. The data was analysed for 3-day mortality, 30-day mortality, hospital admission, and high dependency unit or intensive care unit (HDU/ICU) admission. The analysis was run for both the standard ESI triage method and a local 3-level Helsinki University Hospital (HUH) method. A further analysis was run for both triage methods with age adjustment. Net reclassification improvement values were calculated to demonstrate the effect of age adjustment.

Results
Thirteen thousand seven hundred fifty-nine patients met the study criteria, median age was 57. 3-day mortality AUCs for unadjusted HUH and ESI triage were 0.77 (0.65–0.88) and 0.72 (0.57–0.87); 30-day mortality AUCs were 0.64 (0.59–0.69) and 0.69 (0.64–0.73); hospital admission AUCs were 0.60 (0.68–0.71) and 0.66 (0.65–0.68) and HDU/ICU admission AUCs were 0.67 (0.64–0.70) and 0.82 (0.79–0.86), respectively. Age adjustment improved accuracy for 30-day mortality and hospital admission. With the threshold age of 80, AUCs for 30-day mortality were 0.73 (0.68–0.77) and 0.77 (0.73–0.81) and for hospital admission, 0.66 (0.65–0.67) and 0.72 (0.71–0.73) for the HUH and ESI triage. The effect was similar with all cut off ages.

Conclusion
Moving older adults into a more urgent triage category based on age, improved the triage instruments’ performance slightly in predicting 30-day mortality and hospital admission without excessive increase in patient numbers in the higher triage categories. Age adjustment did not improve HDU/ICU admission or 3-day mortality prediction.
Genotype–Phenotype correlations of SCARB2 associated clinical presentation: a case report and in-depth literature review
Authors: Atasu Burcu , Acarlı Ayse Nur Ozdag , Bilgic Basar , Baykan Betül , Demir Erol , Ozluk Yasemin , Turkmen Aydin , Hauser Ann-Kathrin , Guven Gamze , Hanagasi Hasmet , Gurvit Hakan , Emre Murat , Gasser Thomas , Lohmann Ebba 
Published: March 2022

Abstract
Background
Biallelic pathogenic variants in the SCARB2 gene have been associated with action myoclonus-renal failure (AMRF) syndrome. Even though SCARB2 associated phenotype has been reported to include typical neurological characteristics, depending on the localization and the feature of the pathogenic variants, clinical course and the presentations have been shown to differ.

Case presentation
Whole exome sequencing (WES) analysis revealed a homozygous truncating variant (p.N45MfsX88) in SCARB2 gene in the index case, and subsequent sanger sequencing analysis validated the variant in all affected family members from a Turkish family with the clinical characteristics associated with AMRF and related disorders. Intrafamilial clinical heterogeneity with common features including dysarthria, tremor and proteinuria, and distinct features such as peripheral neuropathy (PNP), myoclonus and seizures between the affected cases, was observed in the family.
In-depth literature review enabled the detailed investigation of the reported variants associated with AMRF and suggested that while the type of the variant did not have a major impact on the course of the clinical characteristics, only the C terminal localization of the pathogenic variant significantly affected the clinical presentation, particularly the age at onset (AO) of the disease.

Conclusions
In this study we showed that biallelic SCARB2 pathogenic variants might cause a spectrum of common and distinct features associated with AMRF. Of those features while the common features include myoclonus (100%), ataxia (96%), tonic clonic seizures (82%), dysarthria (68%), tremor (65%), and renal impairment (62%), the uncommon features involve PNP (17%), hearing loss (6.8%), and cognitive impairment (13.7%). AO has been found to be significantly higher in the carriers of the p.G462DfsX34 pathogenic variant.
SCARB2 pathogenic variants have not been only implicated in AMRF but also in the pathogenesis of Parkinson’s disease (PD) and Gaucher disease (GD), suggesting the importance of genetic and functional studies in the clinical and the diagnostic settings.
Given the proven role of SCARB2 gene in the pathogenesis of AMRF, PD and GD with a wide spectrum of clinical symptoms, investigation of the possible modifiers, such as progranulin and HSP7, has a great importance.
Facilitating stress prevention in micro and small-sized enterprises: protocol for a mixed method study to evaluate the effectiveness and implementation process of targeted web-based interventions
Authors: Engels Miriam , Boß Leif , Engels Judith , Kuhlmann Rebekka , Kuske Johanna , Lepper Sarah , Lesener Lutz , Pavlista Valeria , Diebig Mathias , Lunau Thorsten , Ruhle Sascha A. , Zapkau Florian B. , Angerer Peter , Hoewner Jörg , Lehr Dirk , Schwens Christian , Süß Stefan , Wulf Ines C. , Dragano Nico 
Published: March 2022

Abstract
Background
Workplace-related stress is a major risk factor for mental and physical health problems and related sickness absence and productivity loss. Despite evidence regarding the effectiveness of different workplace-based interventions, the implementation of stress prevention interventions is rare, especially in micro and small-sized enterprises (MSE) with fewer than 50 employees. The joint research project “PragmatiKK”+ aims to identify and address the specific barriers to the implementation of stress prevention interventions in MSE. This study protocol describes a mixed method study design to evaluate the effectiveness of adapted stress prevention interventions and the implementation process via an integrated web-based platform (“System P”) specifically targeted at MSE.

Methods
First, we develop a web-based intervention, which accounts for the specific working conditions in MSE and addresses stress prevention at a structural and behavioral level. Second, we use common methods of implementation research to perform an effect and process evaluation. We analyze the effectiveness of the web-based stress prevention interventions by comparing depressive symptoms at baseline and follow-up (after 6 months and 12 months). Indicators for a successful implementation process include acceptability, adoption, feasibility, reach, dose, and fidelity, which we will measure with quantitative web-based questionnaires and qualitative interviews. We will also analyze the accumulated usage data from the web-based platform.

Discussion
Collecting data on the implementation process and the effectiveness of a web-based intervention will help to identify and overcome common barriers to stress prevention in MSE. This can improve the mental health of employees in MSE, which constitute more than 90% of all enterprises in Germany.
+ Full Project Name: „PragmatiKK - Pragmatische Lösungen für die Implementation von Maßnahmen zur Stressprävention in Kleinst- und Kleinbetrieben “(= Pragmatic solutions for the implementation of stress prevention interventions in micro and small-sized enterprises).

Trial registration
German Register of Clinical Studies (DRKS): DRKS00026154, date of registration: 2021-09-16.