bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small-scale sequencing enables quality assessment of Ribo-Seq data: an example from Arabidopsis cell culture
Authors: Mahboubi Amir , Delhomme Nicolas , Häggström Sara , Hanson Johannes 
Published: August 2021

Abstract
Background
Translation is a tightly regulated process, controlling the rate of protein synthesis in cells. Ribosome sequencing (Ribo-Seq) is a recently developed tool for studying actively translated mRNA and can thus directly address translational regulation. Ribo-Seq libraries need to be sequenced to a great depth due to high contamination by rRNA and other contaminating nucleic acid fragments. Deep sequencing is expensive, and it generates large volumes of data, making data analysis complicated and time consuming.

Methods and results
Here we developed a platform for Ribo-Seq library construction and data analysis to enable rapid quality assessment of Ribo-Seq libraries with the help of a small-scale sequencer. Our data show that several qualitative features of a Ribo-Seq library, such as read length distribution, P-site distribution, reading frame and triplet periodicity, can be effectively evaluated using only the data generated by a benchtop sequencer with a very limited number of reads.

Conclusion
Our pipeline enables rapid evaluation of Ribo-Seq libraries, opening up possibilities for optimization of Ribo-Seq library construction from difficult samples, and leading to better decision making prior to more costly deep sequencing.
The biomechanical effect of preexisting different types of disc herniation in cervical hyperextension injury
Authors: Wang Jian-jie , Xu Meng-lei , Zeng Hui-zi , Zheng Liang-dong , Zhu Shi-jie , Jin Chen , Zeng Zhi-li , Cheng Li-ming , Zhu Rui 
Published: August 2021

Abstract
Objective
Preexisting severe cervical spinal cord compression is a significant risk factor in cervical hyperextension injury, and the neurological function may deteriorate after a slight force to the forehead. There are few biomechanical studies regarding the influence of pathological factors in hyperextension loading condition. The aim of this study is to analyze the effects of preexisting different types of cervical disc herniation and different degrees of compression on the spinal cord in cervical hyperextension.

Method
A 3D finite element (FE) model of cervical spinal cord was modeled. Local type with median herniation, local type with lateral herniation, diffuse type with median herniation, and diffuse type with lateral herniation were simulated in neutral and extention positions. The compressions which were equivalent to 10%, 20%, 30%, and 40% of the sagittal diameter of the spinal cord were modeled.

Results
The results of normal FE model were consistent with those of previous studies. The maximum von Mises stresses appeared in the pia mater for all 32 loading conditions. The maximum von Mises stresses in extension position were much higher than in neutral position. In most cases, the maximum von Mises stresses in diffuse type were higher than in local type.

Conclusion
Cervical spinal cord with preexisting disc herniation is more likely to be compressed in hyperextension situation than in neutral position. Diffuse type with median herniation may cause more severe compression with higher von Mises stresses concentrated at the anterior horn and the peripheral white matter, resulting in acute central cord syndrome from biomechanical point of view.
Sex dependent glial-specific changes in the chromatin accessibility landscape in late-onset Alzheimer’s disease brains
Authors: Barrera Julio , Song Lingyun , Gamache Julia E. , Garrett Melanie E. , Safi Alexias , Yun Young , Premasinghe Ivana , Sprague Daniel , Chipman Danielle , Li Jeffrey , Fradin Hélène , Soldano Karen , Gordân Raluca , Ashley-Koch Allison E. , Crawford Gregory E. , Chiba-Falek Ornit 
Published: August 2021

Abstract
Background
In the post-GWAS era, there is an unmet need to decode the underpinning genetic etiologies of late-onset Alzheimer’s disease (LOAD) and translate the associations to causation.

Methods
We conducted ATAC-seq profiling using NeuN sorted-nuclei from 40 frozen brain tissues to determine LOAD-specific changes in chromatin accessibility landscape in a cell-type specific manner.

Results
We identified 211 LOAD-specific differential chromatin accessibility sites in neuronal-nuclei, four of which overlapped with LOAD-GWAS regions (±100 kb of SNP). While the non-neuronal nuclei did not show LOAD-specific differences, stratification by sex identified 842 LOAD-specific chromatin accessibility sites in females. Seven of these sex-dependent sites in the non-neuronal samples overlapped LOAD-GWAS regions including APOE. LOAD loci were functionally validated using single-nuclei RNA-seq datasets.

Conclusions
Using brain sorted-nuclei enabled the identification of sex-dependent cell type-specific LOAD alterations in chromatin structure. These findings enhance the interpretation of LOAD-GWAS discoveries, provide potential pathomechanisms, and suggest novel LOAD-loci.

Graphical Abstract
Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer
Authors: Xie Chunfeng , Zhou Xu , Liang Chunhua , Li Xiaoting , Ge Miaomiao , Chen Yue , Yin Juan , Zhu Jianyun , Zhong Caiyun 
Published: August 2021

Abstract
Background
Recently, a variety of clinical trials have shown that apatinib, a small-molecule anti-angiogenic drug, exerts promising inhibitory effects on multiple solid tumors, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism of apatinib on NSCLC remains unclear.

Methods
MTT, EdU, AO/EB staining, TUNEL staining, flow cytometry, colony formation assays were performed to investigate the effects of apatinib on cell proliferation, cell cycle distribution, apoptosis and cancer stem like properties. Wound healing and transwell assays were conducted to explore the role of apatinib on migration and invasion. The regulation of apatinib on VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling were detected. Furthermore, we collected conditioned medium (CM) from A549 and H1299 cells to stimulate phorbol myristate acetate (PMA)-activated THP-1 cells, and examined the effect of apatinib on PD-L1 expression in macrophages. The Jurkat T cells and NSCLC cells co-culture model was used to assess the effect of apatinib on T cells activation. Subcutaneous tumor formation models were established to evaluate the effects of apatinib in vivo. Histochemical, immunohistochemical staining and ELISA assay were used to examine the levels of signaling molecules in tumors.

Results
We showed that apatinib inhibited cell proliferation and promoted apoptosis in NSCLC cells in vitro. Apatinib induced cell cycle arrest at G1 phase and suppressed the expression of Cyclin D1 and CDK4. Moreover, apatinib upregulated Cleaved Caspase 3, Cleaved Caspase 9 and Bax, and downregulated Bcl-2 in NSCLC cells. The colony formation ability and the number of CD133 positive cells were significantly decreased by apatinib, suggesting that apatinib inhibited the malignant and stem-like features of NSCLC cells. Mechanistically, apatinib inhibited PD-L1 and c-Myc expression by targeting VEGFR2/STAT3 signaling. Apatinib also inhibited PD-L1 expression in THP-1 derived macrophages stimulated by CM from NSCLC cells. Furthermore, apatinib pretreatment increased CD69 expression and IFN-γ secretion in stimulated Jurkat T cells co-cultured with NSCLC cells. Apatinib also promoted ROS production and inhibited Nrf2 and p62 expression, leading to the autophagic and apoptotic cell death in NSCLC. Moreover, apatinib significantly inhibited tumor growth in vivo.

Conclusion
Our data indicated that apatinib induced autophagy and apoptosis in NSCLC via regulating VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling.
Deterministic transition of enterotypes shapes the infant gut microbiome at an early age
Authors: Xiao Liwen , Wang Jinfeng , Zheng Jiayong , Li Xiaoqing , Zhao Fangqing 
Published: August 2021

AbstractBackgroundThe succession of the gut microbiota during the first few years plays a vital role in human development. We elucidate the characteristics and alternations of the infant gut microbiota to better understand the correlation between infant health and microbiota maturation.ResultsWe collect 13,776 fecal samples or datasets from 1956 infants between 1 and 3 years of age, based on multi-population cohorts covering 17 countries. The characteristics of the gut microbiota are analyzed based on enterotype and an ecological model. Clinical information (n= 2287) is integrated to understand outcomes of different developmental patterns. Infants whose gut microbiota are dominated by Firmicutes andBifidobacteriumexhibit typical characteristics of early developmental stages, such as unstable community structure and low microbiome maturation, while those driven byBacteroidesandPrevotellaare characterized by higher diversity and stronger connections in the gut microbial community. We further reveal a geography-related pattern in global populations. Through ecological modeling and functional analysis, we demonstrate that the transition of the gut microbiota from infants towards adults follows a deterministic pattern; as infants grow up, the dominance of Firmicutes andBifidobacteriumis replaced by that ofBacteroidesandPrevotella, along with shifts in specific metabolic pathways.ConclusionsBy leveraging the extremely large datasets and enterotype-based microbiome analysis, we decipher the colonization and transition of the gut microbiota in infants from a new perspective. We further introduce an ecological model to estimate the tendency of enterotype transitions, and demonstrated that the transition of infant gut microbiota was deterministic and predictable.
CRISTAL (a cluster-randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study): statistical analysis plan
Authors: Sidhu Verinder Singh , Kelly Thu-Lan , Pratt Nicole , Graves Steven , Buchbinder Rachelle , Naylor Justine , de Steiger Richard , Ackerman Ilana , Adie Sam , Lorimer Michelle , Bastiras Durga , Cashman Kara , Harris Ian 
Published: August 2021

Abstract
Background
This a priori statistical analysis plan describes the analysis for CRISTAL.

Methods
CRISTAL (cluster-randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study) aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic venous thromboembolism (VTE) following hip arthroplasty (HA) or knee arthroplasty (KA). The study is nested within the Australian Orthopaedic Association National Joint Replacement Registry. The trial was commenced in April 2019 and after an unplanned interim analysis, recruitment was stopped (December 2020), as the stopping rule was met for the primary outcome.
The clusters comprised hospitals performing > 250 HA and/or KA procedures per annum, whereby all adults (> 18 years) undergoing HA or KA were recruited. Each hospital was randomised to commence with aspirin, orally, 85–150 mg daily or LMWH (enoxaparin), 40 mg, subcutaneously, daily within 24 h postoperatively, for 35 days after HA and 14 days after KA. Crossover was planned once the registration target was met for the first arm.
The primary end point is symptomatic VTE within 90 days. Secondary outcomes include readmission, reoperation, major bleeding and death within 90 days, and reoperation and patient-reported pain, function and health status at 6 months.
The main analyses will focus on the primary and secondary outcomes for patients undergoing elective primary total HA and KA for osteoarthritis. The analysis will use an intention-to-treat approach with cluster summary methods to compare treatment arms. As the trial stopped early, analyses will account for incomplete cluster crossover and unequal cluster sizes.

Conclusions
This paper provides a detailed statistical analysis plan for CRISTAL.

Trial registration
Australian and New Zealand Clinical Trials Registry ACTRN12618001879257. Registered on 19/11/2018.
Patient- and physician-reported outcomes from two phase 3 randomized studies (RAJ3 and RAJ4) of peficitinib (ASP015K) in Asian patients with rheumatoid arthritis
Authors: Tanaka Yoshiya , Takeuchi Tsutomu , Izutsu Hiroyuki , Kaneko Yuichiro , Kato Daisuke , Fukuda Musashi , Rokuda Mitsuhiro , Schultz Neil M. 
Published: August 2021

Abstract
Background
Peficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety in the treatment of patients with rheumatoid arthritis (RA). This study evaluated the effect of peficitinib on patient- and physician-reported outcomes in Asian patients with RA and an inadequate response to prior disease-modifying antirheumatic drugs (DMARDs).

Methods
Patients from two randomized, placebo-controlled, double-blind, phase 3 trials (RAJ3 and RAJ4) received once-daily peficitinib 100 mg, peficitinib 150 mg, or placebo, alone or in combination with DMARDs (RAJ3), or in combination with methotrexate (RAJ4). Mean changes in Work Productivity and Activity Impairment (WPAI) questionnaire domain scores from baseline, and percentages of patients achieving minimal clinically important differences (MCIDs) for patient- and physician-reported outcomes (WPAI, Health Assessment Questionnaire – Disability Index [HAQ-DI], and Subject’s Global Assessment of Pain [SGAP]), and Physician’s Global Assessment of disease activity (PGA) were evaluated at weeks 4, 8, 12, and 12/early termination (ET).

Results
Data from 1025 patients were analyzed. At week 12/ET in both studies, patients who received peficitinib 100 mg or 150 mg reported significantly improved WPAI domain scores from baseline (except for absenteeism in RAJ4) compared with placebo (both doses, p<0.05). A higher proportion of peficitinib- versus placebo-treated patients achieved MCID in WPAI, HAQ-DI, SGAP, and PGA in studies RAJ3 and RAJ4. Significant differences with peficitinib versus placebo were evident in both studies as early as week 4 in HAQ-DI (peficitinib 150 mg only), SGAP, and PGA, and week 8 in WPAI loss of work productivity and daily activity impairment. At week 12/ET, significantly higher proportions of patients receiving peficitinib versus placebo achieved MCID in HAQ-DI, SGAP, PGA, and WPAI domains of presenteeism (RAJ3 only), loss of work productivity (RAJ3 only), and daily activity impairment (p<0.05 for all comparisons).

Conclusions
Peficitinib 100 mg or 150 mg administered daily over 12 weeks resulted in clinically meaningful improvements in outcomes that are important to RA patients, including pain, physical function, and work productivity and activity. These observations were reinforced through similar improvements in physicians’ rating of disease activity.

Trial registration
RAJ3: ClinicalTrials.gov, NCT02308163, registered 4 December 2014.
RAJ4: ClinicalTrials.gov, NCT02305849, registered 3 December 2014.
Incidence and severity of G6PI-induced arthritis are not increased in genetically distinct mouse strains upon aging
Authors: Andreas Nico , Müller Sylvia , Templin Nicole , Jordan Paul M. , Schuhwerk Harald , Müller Michael , Gerstmeier Jana , Miek Laura , Andreas Saskia , Werz Oliver , Kamradt Thomas 
Published: August 2021

Abstract
Background
The incidence of rheumatoid arthritis is correlated with age. In this study, we analyzed the association of the incidence and severity of glucose-6-phosphate isomerase (G6PI)-induced arthritis with age in two different mouse strains.

Methods
Young and very old mice from two different arthritis-susceptible wild-type mouse strains were analyzed after a single subcutaneous injection of G6PI s.c. The metabolism and the function of synoviocytes were analyzed in vitro, the production of bioactive lipid mediators by myeloid cells and synoviocytes was assessed in vitro and ex vivo by UPLC-MS-MS, and flow cytometry was used to verify age-related changes of immune cell composition and function.

Results
While the severity of arthritis was independent from age, the onset was delayed in old mice. Old mice showed common signs of immune aging like thymic atrophy associated with decreased CD4+ effector T cell numbers. Despite its decrease, the effector T helper (Th) cell compartment in old mice was reactive and functionally intact, and their Tregs exhibited unaltered suppressive capacities. In homeostasis, macrophages and synoviocytes from old mice produced higher amounts of pro-inflammatory cyclooxygenase (COX)-derived products. However, this functional difference did not remain upon challenge in vitro nor upon arthritis reactions ex vivo.

Conclusion
While old mice show a higher baseline of inflammatory functions, this does not result in increased reaction towards self-antigens in arthritis-susceptible mouse strains. Together, our data from two different mouse strains show that the susceptibility for G6PI-induced arthritis is not age-dependent.
Maternal age at first childbirth and under-five morbidity in sub-Saharan Africa: analysis of cross-sectional data of 32 countries
Authors: Ahinkorah Bright Opoku 
Published: August 2021

Abstract
Background
The prevalence of childhood morbidity remains high in low-and middle-income countries, including sub-Saharan Africa (SSA). In this study, the association between maternal age at first childbirth and under-five morbidity in SSA was examined.

Methods
This was a cross-sectional study involving nationally-representative data from the most recent Demographic and Health Surveys conducted in 32 countries in SSA from 2010 to 2019. A sample size of 311,603 mothers of children under-five was considered. The outcome variable for this study was under-five morbidity. This variable was derived from the experience of fever, cough, and diarrhoea among children under-five. Both multilevel and binary logistic regression models were used to test the hypothesis that adolescent childbirth is associated with under-five morbidity. The results were presented as crude odds ratios (cORs) and adjusted odds ratios (aORs), with 95 % confidence intervals (CIs).

Results
Children born to mothers whose first childbirth occurred at < 20 years were 16 % times more likely to suffer from under-five morbidity, compared to those whose mothers’ first childbirth occurred at age ≥ 20 years [cOR = 1.16; CI = 1.13–1.19], and this persisted but with reduced odds after controlling for covariates [aOR = 1.10; CI = 1.07–1.12]. At the country level, children born to mothers whose first childbirth occurred at < 20 years were more likely to suffer from under-five morbidity, compared to those whose mothers’ first childbirth occurred at age ≥ 20 years in Angola, Burundi, Congo DR, Guinea, Kenya, and Uganda.

Conclusions
In this study, an association between adolescent childbirth and morbidity in children under five in SSA has been established. The study concludes that under-five morbidity is higher among children born to mothers whose first childbirth occurred before 20 years compared to those whose mothers’ first childbirth occurred at 20 years and above. The findings indicate that in order to reduce under-five morbidity, there is the need to deal with adolescent childbearing through cultural and social change, coupled with engagement of adolescents and stakeholders in adolescent sexual and reproductive health programmes.
Diversifying a resource-dependent economy: private–public relationships in the Kuwaiti economy
Authors: Gelan Ayele , Hewings Geoffrey J. D. , Alawadhi Ahmad 
Published: August 2021

AbstractThe Kuwaiti economy is characterized by two major structural imbalances—heavy dependence on oil production and dominance of the public ownership. Kuwait has struggled over the years to implement a two-pronged development strategy —diversifying the country’s economic base away from the oil sector and promoting private sector development. This paper explores the economic impact of some policy reform options currently being considered. It employs a unique set of input–output tables, derived from supply–use tables, that distinguishes transactions made by private and public enterprises as well as providing a matrix of imports by industry. The public–private sector interdependence analysis revealed interesting results regarding sectoral differences in strengths of forward and backward linkages. For instance, the findings indicated that the strength of the publicly owned oil sectors lie in their forward linkages, supplying other sectors with their outputs, but their backward linkages is weak. On the other hand, the chemicals industry is identified as one of a few sectors with balanced and relatively strong forward and backward linkages in both public and private sector. The policy analyses conducted in this paper are highly relevant to the ongoing policy debate in Kuwait over the design of the economic reform programs. The public–private linkage analysis has revealed insights into policy synergies through which one instrument can affect more than one policy target.
Monitoring and assessment of endangered UNESCO World Heritage Sites using space technology: a case study of East Rennell, Solomon Islands
Authors: Huo Sijia , Wang Mengmeng , Chen Guolong , Shu Huiqin , Yang Ruixia 
Published: August 2021

Abstract
Space technology offers effective tools to monitor the status of World Natural Heritage sites. East Rennell Island, which covers approximately 37,000 hectares (ha) and a marine area extending three nautical miles into the sea, was added to the list of endangered World Natural Heritage sites in 2013. Deforestation and natural disasters have increasingly threatened sustainable development on the island. Based on analyses of multi-source time series of remote sensing data (e.g., MODIS and Worldview), the forest cover change on Rennell Island from 2000 to 2020 and its future trends were mapped and analysed using Sen + Mann–Kendall and Hurst index models. A land cover classification system derived from high-resolution Worldview images was developed as a baseline for monitoring and analysing future forest cover changes on the island. Our results showed that (1) the areas of vegetation degradation and improvement were basically equal from 2000 to 2020. (2) The forest cover change trend had weak continuity, and significant improvements could be achieved in areas with damaged vegetation given sufficient protection measures and financial input. (3) This heritage site has a strong vegetation regeneration ability, and human activities such as mining, logging, and road construction, which could greatly disturb the unique ecosystem, should be restricted.