bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges at the APOE locus: a robust quality control approach for accurate APOE genotyping
Authors: Belloy Michael E. , Eger Sarah J. , Le Guen Yann , Damotte Vincent , Ahmad Shahzad , Ikram M. Arfan , Ramirez Alfredo , Tsolaki Anthoula C. , Rossi Giacomina , Jansen Iris E. , de Rojas Itziar , Parveen Kayenat , Sleegers Kristel , Ingelsson Martin , Hiltunen Mikko , Amin Najaf , Andreassen Ole , Sánchez-Juan Pascual , Kehoe Patrick , Amouyel Philippe , Sims Rebecca , Frikke-Schmidt Ruth , van der Flier Wiesje M. , Lambert Jean-Charles ,   for the European Alzheimer & Dementia BioBank (EADB), He Zihuai , Han Summer S. , Napolioni Valerio , Greicius Michael D. 
Published: February 2022

Abstract
Background
Genetic variants within the APOE locus may modulate Alzheimer’s disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE. The APOE locus however remains relatively poorly understood in AD, owing to multiple challenges that include its complex linkage structure and uncertainty in APOE*2/3/4 genotype quality. Here, we present a novel APOE*2/3/4 filtering approach and showcase its relevance on AD risk association analyses for the rs439401 variant, which is located 1801 base pairs downstream of APOE and has been associated with a potential regulatory effect on APOE.

Methods
We used thirty-two AD-related cohorts, with genetic data from various high-density single-nucleotide polymorphism microarrays, whole-genome sequencing, and whole-exome sequencing. Study participants were filtered to be ages 60 and older, non-Hispanic, of European ancestry, and diagnosed as cognitively normal or AD (n = 65,701). Primary analyses investigated AD risk in APOE*4/4 carriers. Additional supporting analyses were performed in APOE*3/4 and 3/3 strata. Outcomes were compared under two different APOE*2/3/4 filtering approaches.

Results
Using more conventional APOE*2/3/4 filtering criteria (approach 1), we showed that, when in-phase with APOE*4, rs439401 was variably associated with protective effects on AD case-control status. However, when applying a novel filter that increases the certainty of the APOE*2/3/4 genotypes by applying more stringent criteria for concordance between the provided APOE genotype and imputed APOE genotype (approach 2), we observed that all significant effects were lost.

Conclusions
We showed that careful consideration of APOE genotype and appropriate sample filtering were crucial to robustly interrogate the role of the APOE locus on AD risk. Our study presents a novel APOE filtering approach and provides important guidelines for research into the APOE locus, as well as for elucidating genetic interaction effects with APOE*2/3/4.
N-myc downstream regulated gene 1 suppresses osteoblast differentiation through inactivating Wnt/β-catenin signaling
Authors: Shi Xiaoli , Cen Yunzhu , Shan Liying , Tian Lijie , Zhu Endong , Yuan Hairui , Li Xiaoxia , Liu Ying , Wang Baoli 
Published: February 2022

Abstract
Background
N-myc downstream regulated gene 1 (NDRG1) plays a role in a variety of biological processes including differentiation of osteoclasts. However, it is not known if and how NDRG1 regulates osteogenic differentiation of marrow stromal progenitor cells.

Methods
Gene expression profiling analysis was performed to study the expression level of Ndrg1 during osteogenic and adipogenic differentiation. Gain-of-function and/or loss-of function experiments were carried out to study the role of NDRG1 in the proliferation and differentiation of marrow stromal progenitor cells and the mechanism underlying the function was investigated. Finally, in vivo transfection of Ndrg1 siRNA was done and its effect on osteogenic and adipogenic differentiation in mice was explored.

Results
Gene expression profiling analysis revealed that NDRG1 level was regulated during osteogenic and adipogenic differentiation of progenitor cells. The functional experiments demonstrated that NDRG1 negatively regulated the cell growth, and reciprocally modulated the osteogenic and adipogenic commitment of marrow stromal progenitor cells, driving the cells to differentiate toward adipocytes at the expense of osteoblast differentiation. Moreover, NDRG1 interacted with low-density lipoprotein receptor-related protein 6 (LRP6) in the stromal progenitor cells and inactivated the canonical Wnt/β-catenin signaling cascade. Furthermore, the impaired differentiation of progenitor cells induced by Ndrg1 siRNA could be attenuated when β-catenin was simultaneously silenced. Finally, in vivo transfection of Ndrg1 siRNA to the marrow of mice prevented the inactivation of canonical Wnt signaling in the BMSCs of ovariectomized mice, and ameliorated the reduction of osteoblasts on the trabeculae and increase of fat accumulation in the marrow observed in the ovariectomized mice.

Conclusion
This study has provided evidences that NDRG1 plays a role in reciprocally modulating osteogenic and adipogenic commitment of marrow stromal progenitor cells through inactivating canonical Wnt signaling.
Long-chain glucomannan supplementation modulates immune responsiveness, as well as intestinal microbiota, and impacts infection of broiler chickens with Salmonella enterica serotype Enteritidis
Authors: Meijerink Nathalie , de Oliveira Jean E. , van Haarlem Daphne A. , Lamot David M. , Velkers Francisca C. , Smidt Hauke , Stegeman J. Arjan , Rutten Victor P. M. G. , Jansen Christine A. 
Published: February 2022

AbstractThe zoonotic pathogen Salmonella enterica serotype Enteritidis (SE) causes severe disease in young chickens. Restriction on antibiotic use requires alternative SE control strategies such as nutritional solutions to improve the resistance of chickens. In this study, chickens were fed long-chain glucomannan (GM) or standard diet and challenged with SE at seven days of age. During 21 days post-infection (dpi), we determined numbers and responsiveness of natural killer (NK) and T cells in ileum and spleen, and SE-specific antibody titers in serum. Microbiota compositions in ileum and caeca were determined, as well as correlations of these with numbers and function of immune cells. Some of the samples in the control group had numerically higher CFUs than the GM-treated group. In addition, the relative abundance of SE based on DNA assessment was significantly lower at 21 dpi upon GM supplementation. At 3 dpi, numbers of intraepithelial NK cells were significantly higher, while activation of intraepithelial NK cells (7 dpi), numbers of intraepithelial cytotoxic CD8+ T cells (14 dpi) and SE-specific antibodies (14 dpi) were numerically higher. Furthermore, relative abundance of the commensal lactic acid bacteria (LAB) significantly increased with GM supplementation post-infection. Higher relative abundance of streptococci was associated with reduced SE in ileal and caecal contents at 21 dpi. Relative abundance of streptococci negatively correlated with SE counts and positively correlated with NK cell activation and SE-specific antibodies, which suggests involvement of the commensal LAB in NK cell responsiveness. These results indicate that GM supplementation modulates the immune system, intestinal microbiota and impacts SE infection of young chickens.
Practices in sedation, analgesia, mobilization, delirium, and sleep deprivation in adult intensive care units (SAMDS-ICU): an international survey before and during the COVID-19 pandemic
Authors: Luz Mariana , Brandão Barreto Bruna , de Castro Roberta Esteves Vieira , Salluh Jorge , Dal-Pizzol Felipe , Araujo Caio , De Jong Audrey , Chanques Gérald , Myatra Sheila Nainan , Tobar Eduardo , Gimenez-Esparza Vich Carolina , Carini Federico , Ely Eugene Wesley , Stollings Joanna L. , Drumright Kelly , Kress John , Povoa Pedro , Shehabi Yahya , Mphandi Wilson , Gusmao-Flores Dimitri 
Published: February 2022

Abstract
Background
Since the publication of the 2018 Clinical Guidelines about sedation, analgesia, delirium, mobilization, and sleep deprivation in critically ill patients, no evaluation and adequacy assessment of these recommendations were studied in an international context. This survey aimed to investigate these current practices and if the COVID-19 pandemic has changed them.

Methods
This study was an open multinational electronic survey directed to physicians working in adult intensive care units (ICUs), which was performed in two steps: before and during the COVID-19 pandemic.

Results
We analyzed 1768 questionnaires and 1539 (87%) were complete. Before the COVID-19 pandemic, we received 1476 questionnaires and 292 were submitted later. The following practices were observed before the pandemic: the Visual Analog Scale (VAS) (61.5%), the Behavioral Pain Scale (BPS) (48.2%), the Richmond Agitation Sedation Scale (RASS) (76.6%), and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) (66.6%) were the most frequently tools used to assess pain, sedation level, and delirium, respectively; midazolam and fentanyl were the most frequently used drugs for inducing sedation and analgesia (84.8% and 78.3%, respectively), whereas haloperidol (68.8%) and atypical antipsychotics (69.4%) were the most prescribed drugs for delirium treatment; some physicians regularly prescribed drugs to induce sleep (19.1%) or ordered mechanical restraints as part of their routine (6.2%) for patients on mechanical ventilation; non-pharmacological strategies were frequently applied for pain, delirium, and sleep deprivation management. During the COVID-19 pandemic, the intensive care specialty was independently associated with best practices. Moreover, the mechanical ventilation rate was higher, patients received sedation more often (94% versus 86.1%, p < 0.001) and sedation goals were discussed more frequently in daily rounds. Morphine was the main drug used for analgesia (77.2%), and some sedative drugs, such as midazolam, propofol, ketamine and quetiapine, were used more frequently.

Conclusions
Most sedation, analgesia and delirium practices were comparable before and during the COVID-19 pandemic. During the pandemic, the intensive care specialty was a variable that was independently associated with the best practices. Although many findings are in accordance with evidence-based recommendations, some practices still need improvement.
Effects of logging on the trade-off between seed and sprout regeneration of dominant woody species in secondary forests of the Natural Forest Protection Project of China
Authors: Li Rong , Yan Qiaoling , Xie Jin , Wang Jing , Zhang Ting , Zhu Jiaojun 
Published: February 2022

Abstract
Background
Promoting natural regeneration (including seed and sprout regeneration) of dominant woody species is essential for restoring secondary forests. However, such restoration processes have been decelerated by the enclosure under Natural Forest Protection Project of China (NFPP). It remains unclear how to implement appropriate management measures (e.g., whether to apply logging and the suitable intensity) to facilitate natural regeneration according to the responses of two regeneration modes to management measures. We monitored the early stages of seed regeneration (seed rain, soil seed bank, and 1–3-year-old seedlings) and sprout regeneration (stump sprout rate, stump survival rate, probability of sprouting, and number of sprouts per stump) over the first 3 years (2017–2019) after logging under three intensity regimes (control [0%], 25%, and 50% logging intensity) in secondary forests.

Results
The seed rain density decreased markedly, seedling density increased insignificantly after logging, and logging promoted seedling survival at an increasing conversion rate of 3-year-old seedlings (37.5% under 0%, 100% under 25%, and 80.95% under 50% logging) compared to those of the control. The proportion of 3-year-old seedlings increased with logging intensity and was the highest (16.2%) at 50% logging intensity. Sprout density was not affected by logging intensity, however, under 25% and 50% logging, it decreased by 27% and 6% in 2018, and by 37% and 33% in 2019, respectively. Seedling density was 41.65- and 15.31-fold higher than that of sprouts in the 50% and 25% logging treatments, respectively. Based on the relative contributions of the two regeneration modes after logging, three groups of natural regeneration patterns were classified for dominant woody species in temperate secondary forests, i.e., seed regeneration preference (Betula dahurica, Carpinus cordata and Fraxinus mandshurica), sprout regeneration preference (Acer mono and Acer pseudosieboldianum) and no preference (Quercus mongolica, Fraxinus rhynchophylla, and Juglans mandshurica).

Conclusion
In addition to enclosure, appropriate logging can be applied according to the responses of various natural regeneration patterns of dominant woody species to logging in temperate secondary forests under the NFPP.
Entrepreneurship in Jordan: the eco-system of the Social Entrepreneurship Support Organizations (SESOs)
Authors: Jarrar Amani 
Published: February 2022

AbstractThis study aims at assessing the Social Entrepreneurship Support Organizations (SESOs) in Jordan with an updated eco-system reflecting the better resourced Social Entrepreneurship eco-system characterized with comprehensive information; covering the stakeholders’ identification data, ongoing projects and initiatives, work scope, and their targeted groups, accurate data based on a well-developed survey and analysis of the survey data by the authors’ experience in this filed. This study also aims at assessing the SESOs capacity by coincide their desired needs and their actual needs and limit the social innovation concept variation among the different institutions in the ecosystem. This study also provides a survey analysis for the Social Entrepreneurship Support Organizations (SESOs); as an attempt to identify their characteristics and roles in Jordan by adopting the methodology of qualitative and quantitative analysis approach. Results show that (57.89%) of the SESO’s in Jordan have dedicated programs that focus on women's inclusion, and that (68.42%) are hiring more than 50% in their staff. Besides that, results also show that (59.65%) of the SESO’s in Jordan did not dedicate programs for people with disabilities (PWD); which is a high portion in neglecting this segment of people. Besides that (54.39%) do not have designed facilities friendly using for people with disabilities. Moreover, results show that (73.68%) had dedicated programs for youth with different age groups, and (77.19%) of the SESO’s in Jordan had attempted to identify, understand, and actively removing barriers that exist for certain groups of young people in society. Moreover, (70.18%) of the SESO’s in Jordan had organized specific outreach mechanisms to identify, meet, engage, and/or serve different population groups. Finally, results show that (38.60%) of the SESO’s in Jordan had dedicated programs for refugees.
Relationship between faculty characteristics and their entrepreneurial orientation in higher education institutions in Kuwait
Authors: Abidi Oualid , Nimer Khalil , Bani-Mustafa Ahmed , Toglaw Sam 
Published: February 2022

AbstractConsidering intrapreneurship theory, this study aims to examine the extent to which the entrepreneurial orientation of faculty employed at Kuwaiti higher education institutions differ across their individual-level attributes. Faculty entrepreneurial orientation will be assessed at three levels, i.e., innovativeness, risk-taking, and proactivity. For this purpose, we surveyed a sample of 291 faculty from Kuwaiti colleges and universities. The core constructs were operationalized using scales validated in previous studies. The hypothesized relationships were tested using the structural equation modeling method. Our findings indicate that while female faculty are more proactive than men, males are innovative and risk-takers to some extent. Moreover, Ph.D. holders are more proactive and innovative than Master’s degree holders. The relationship between specialization and both innovativeness and risk-taking is significant only for business, but not for engineering. Teaching experience is more positively correlated with faculty proactivity. The number of scientific publications is negatively associated with faculty risk-taking propensity. Additionally, faculty who cumulated significant industry experience are proactive in identifying long-term opportunities and threats for their institutions. Having earned professional certifications is positively related to some aspects of innovativeness and proactivity. Finally, faculty who received their latest degree from a non-accredited institution are more active in realizing ideas at work.
What are the outcomes of marine site protection on poverty of coastal communities in Southeast Asia? A systematic review protocol
Authors: Zain Mohd Aizat , Suhaimi Julia , Dahlui Maznah , Goh Hong Ching , Then Amy Yee-Hui , Yakub Nur Asyikin , Noor Mohd Iqbal Mohd , Garside Ruth , Eales Jacqualyn , Jose Edgar , Kari Fatimah 
Published: February 2022

Abstract
Background
Many conservation management interventions have been set up to bring win–win outcomes for both biodiversity conservation and the well-being of the local communities. Nevertheless, the implementation process of marine protected areas (MPAs) can generate unexpected outcomes and fail to reach its objectives in addressing communities’ challenges. Therefore, it is crucial to have a better understanding of how MPAs influence the socioeconomic aspects of the coastal communities. This paper describes the protocol to conduct a systematic review which aims to explore and review the evidence that reflects the outcomes of marine site protection on poverty reduction in terms of economic and material living standards among the coastal communities in Southeast Asia. The review question is “What are the outcomes of marine site protection implementation on poverty in terms of material and economic living standards of coastal communities in Southeast Asia?”.

Methods
The systematic review uses rigorous search strategies and selection methods based on pre-defined eligibility criteria to identify and examine published journal articles and grey literature that are available on the review topic. Relevant studies and grey literature will be extracted from a recent systematic map of the evidence documenting the effect of marine or coastal nature conservation or natural resource management activities on human well-being in Southeast Asia. We will search online databases including Web of Science Core Collection, Ovid Medline®, Environmental Complete, Scopus, as well as Google Scholar and sources of grey literature for any additional literature available since the evidence map was created. For this review, the populations of interest are from coastal communities in the Southeast Asia region. Comparators to marine site protection will be no intervention and/or pre-MPA implementation. The economic and material living standards, which are the poverty domains, will be evaluated as outcomes. Once we have identified relevant literature, we will perform a critical appraisal, data extraction, and synthesis appropriate to the type of literature found, to investigate the effect of marine site protection on poverty reduction.
Geographical differences of carbapenem non-susceptible Enterobacterales and Acinetobacter spp. in Germany from 2017 to 2019
Authors: von Laer Anja , Eckmanns Tim , Zacher Benedikt , Pfennigwerth Niels , Gatermann Sören G. , Reichert Felix , Diercke Michaela , Steffen Gyde , Altmann Doris , Reuss Annicka 
Published: February 2022

Abstract
Background
Since May 2016, infection and colonisation with carbapenem non-susceptible Acinetobacter spp. (CRA) and Enterobacterales (CRE) have to be notified to health authorities in Germany. The aim of our study was to assess the epidemiology of CRA and CRE from 2017 to 2019 in Germany, to identify risk groups and to determine geographical differences of CRA and CRE notifications.

Methods
Cases were notified from laboratories to local public health authorities and forwarded to state and national level. Non-susceptibility was defined as intermediate or resistant to ertapenem, imipenem, or meropenem excluding intrinsic bacterial resistance or the detection of a carbapenemase gene. We analysed CRA and CRE notifications from 2017, 2018 and 2019 per 100,000 inhabitants (notification incidence), regarding their demographic, clinical and laboratory information. The effect of regional hospital-density on CRA and CRE notification incidence was estimated using negative binomial regression.

Results
From 2017 to 2019, 2278 CRA and 12,282 CRE cases were notified in Germany. CRA and CRE cases did not differ regarding demographic and clinical information, e.g. proportion infected. The notification incidence of CRA declined slightly from 0.95 in 2017 to 0.86 in 2019, whereas CRE increased from 4.23 in 2017 to 5.72 in 2019. The highest CRA and CRE notification incidences were found in the age groups above 70 years. Infants below 1 year showed a high CRE notification incidence, too. Notification incidences varied between 0.10 and 2.86 for CRA and between 1.49 and 9.99 for CRE by federal state. The notification incidence of CRA and CRE cases increased with each additional hospital per district.

Conclusion
The notification incidence of CRA and CRE varied geographically and was correlated with the number of hospitals.The results support the assumption that hospitals are the main driver for higher CRE and CRA incidence. Preventive strategies and early control measures should target older age groups and newborns and areas with a high incidence.
A new short version of the Cognitive Therapy Scale Revised (CTSR-4): preliminary psychometric evaluation
Authors: Alfonsson Sven , Karvelas Georgios , Linde Johanna , Beckman Maria 
Published: February 2022

Abstract
Background
The value of using comprehensive but cumbersome coding instruments to assess therapeutic competency is unclear. Shorter, more general instruments may enable more research in this important area. The aim of this study was therefore to psychometrically evaluate a shorter version of the Cognitive Therapy Scale-Revised (CTSR) and to compare it with the full-length version.

Methods
A four-item coding instrument (the CTSR-4) was derived from the CTSR. Four experienced psychotherapists used the CTSR-4 to assess 50 fifteen-minutes samples from audio-recorded CBT sessions. The criterion validity of the CTSR-4 was analyzed by comparing the results with previously expert-rated CTSR scores from the same sessions, and the inter-rater agreement between the three coders was calculated.

Results
The CTSR-4 showed good criterion validity (ICC = .71–.88) when compared to the expert ratings of the complete CTSR, and the inter-rater agreement was adequate (ICC = .64–.79).

Conclusions
A condensed version of the CTSR, used to assess CBT competence from shorter samples of therapy sessions, is moderately reliable and may provide similar results as the full-length version. According to preliminary analyses, the CTSR-4 has potential as a low-cost alternative to assess CBT competency in both research and psychotherapist training.