bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of LINC01419 in regulating the cell stemness in lung adenocarcinoma through recruiting EZH2 and regulating FBP1 expression
Authors: Chen Zhao , Tang Weijian , Zhou Yuhan , He Zhengfu 
Published: September 2022

Abstract
Background
Recent years have witnessed a growing academic interest in the effects of lncRNAs on tumors. LINC01419 is found to facilitate proliferation and metastasis of lung adenocarcinoma (LUAD) cells, but there is a great deal of uncertainty about how LINC01419 works on LUAD cell stemness. For this reason, the focus of this research is centered on the regulatory impact of LINC01419 on LUAD cell stemness.

Methods
For the detection of the expression level of LINC01419 in LUAD, qRT-PCR was performed. And how oe-LINC01419 and sh-LINC01419 affected LUAD cell proliferation as well as stem cell sphere-formation were examined by CCK-8 and cell sphere-forming assays. In addition, whether LINC01419 could recruit EZH2 and regulate FBP1 expression were determined by bioinformatics analysis, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP). Western blot was utilized to detect the protein expression levels of FBP1, CD44, CD133, and ALDH-1 as well.

Results
On the basis of the findings from those assays, an up-regulation of LINC01419 level was demonstrated in LUAD cell lines, and a remarkable upregulation of it in CD44 + LUAD cells. In LUAD cells, proliferation and stem cell sphere-formation that were attenuated by LINC01419 knockdown were discovered to be facilitated by LINC01419 overexpression. And a binding relationship between LINC01419 and EZH2 was determined by RIP assay. Besides, EZH2 was capable of binding to FBP1 promoter region, as found by ChIP-PCR assay. Finally, it was demonstrated by in vitro experiments that LINC01419 could inhibit FBP1 expression by recruiting EZH2, resulting in promotion of LUAD cell proliferation and stemness.

Significance
To summarize, our findings demonstrate a cancer-promoting role of LINC01419 in LUAD. LINC01419, by recruiting EZH2 and regulating FBP1 expression, contributes to LUAD cell stemness. According to these findings, the potential of LINC01419 to be the target for LUAD treatment is hence determined, which also adds more possibility to the enrichment of therapeutic strategies for lung cancer stem cells.
Dersimelagon, a novel oral melanocortin 1 receptor agonist, demonstrates disease-modifying effects in preclinical models of systemic sclerosis
Authors: Kondo Masahiro , Suzuki Tsuyoshi , Kawano Yuko , Kojima Shinji , Miyashiro Masahiko , Matsumoto Atsuhiro , Kania Gabriela , Błyszczuk Przemysław , Ross Rebecca L. , Mulipa Panji , Del Galdo Francesco , Zhang Yun , Distler Jörg H. W. 
Published: September 2022

Abstract
Background
Activation of melanocortin 1 receptor (MC1R) is known to exert broad anti-inflammatory and anti-fibrotic effects. The purpose of this study is to investigate the potential of dersimelagon, a novel oral MC1R agonist, as a therapeutic agent for systemic sclerosis (SSc).

Methods
The effects of dersimelagon phosphoric acid (MT-7117) on skin fibrosis and lung inflammation were evaluated in bleomycin (BLM)-induced SSc murine models that were optimized for prophylactic and therapeutic evaluation. Microarray-based gene expression analysis and serum protein profiling were performed in the BLM-induced SSc models. The effect of MT-7117 on transforming growth factor-β (TGF-β)-induced activation of human dermal fibroblasts was evaluated in vitro. Immunohistochemical analyses of MC1R expression in the skin of SSc patients were performed.

Results
Prophylactic treatment with MT-7117 (≥ 0.3 mg/kg/day p.o.) significantly inhibited skin fibrosis and lung inflammation, and therapeutic treatment with MT-7117 (≥ 3 mg/kg/day p.o.) significantly suppressed the development of skin fibrosis in the BLM-induced SSc models. Gene array analysis demonstrated that MT-7117 exerts an anti-inflammatory effect via suppression of the activation of inflammatory cells and inflammation-related signals; additionally, vascular dysfunction was extracted as the pathology targeted by MT-7117. Serum protein profiling revealed that multiple SSc-related biomarkers including P-selectin, osteoprotegerin, cystatin C, growth and differentiation factor-15, and S100A9 were suppressed by MT-7117. MT-7117 inhibited the activation of human dermal fibroblasts by suppressing TGF-β-induced ACTA2 (encoding α-smooth muscle actin) mRNA elevation. MC1R was expressed by monocytes/macrophages, neutrophils, blood vessels (endothelial cells), fibroblasts, and epidermis (keratinocytes) in the skin of SSc patients, suggesting that these MC1R-positive cells could be targets for MT-7117.

Conclusions
MT-7117 demonstrates disease-modifying effects in preclinical models of SSc. Investigations of its mechanism of action and target expression analyses indicate that MT-7117 exerts its positive effect by affecting inflammation, vascular dysfunction, and fibrosis, which are all key pathologies of SSc. The results of the present study suggest that MT-7117 is a potential therapeutic agent for SSc. A phase 2 clinical trial investigating the efficacy and tolerability of MT-7117 in patients with early, progressive diffuse cutaneous SSc is currently in progress.
Posterior lumbar interbody fusion for dysplastic lumbar spondylolisthesis with high-grade slippage in two adolescent siblings: two case reports
Authors: Tatsumura Masaki , Funayama Toru , Eto Fumihiko , Nagashima Katsuya , Takeuchi Yosuke , Yamazaki Masashi 
Published: September 2022

Abstract
Background
Lumbar spondylolisthesis is reported to present with a familiar pattern, with the dysplastic type of spondylolysis being minor but more hereditary than the isthmic type. Siblings presenting during adolescence with neurological symptoms owing to high-grade dysplastic-type spondylolisthesis are rare.

Case presentation
The older brother suffered from left leg pain and numbness and dysesthesia of the right posterior thigh and calf and could not walk without a crutch at the age of 15 years. He had canal stenosis with disc bulging and dysplastic bilateral facet joint at L5/S1. The L5 vertebral body was slipped anterior downward to S1, with a round-shaped S1 cranial endplate. We diagnosed dysplastic-type spondylolisthesis and performed posterior lumbar interbody fusion at L5/S with mild reduction and sublaminar wiring at L4/5. The younger brother had no neurological symptoms at age 14 years but suffered from bilateral lower leg numbness at age 18 years. He had canal stenosis with disc bulging at L4/5 and L5/S1 and dysplastic bilateral facet joint at L5/S1 with right pars defect. The L5 vertebral body was vertically displaced anterior to the S1 vertebral body, with an S1 round-shaped cranial endplate. We diagnosed dysplastic-type spondylolisthesis, and posterior lumbar interbody fusion at L4/5 and L5/S with reduction was performed. Their neurological symptoms of the lower legs disappeared, and interbody bone fusion was obtained.

Conclusions
The surgical technique for high-grade dysplastic spondylolisthesis remains controversial in terms of in situ fusion versus reduction. We recommend that surgery be performed promptly at the end of bone maturation because neurological symptoms often appear at the end of bone maturation. Because high-grade slips are rare but siblings may be present, the sibling should also be screened when dysplastic spondylolisthesis is detected.
Spatial optimization of genetic thinning in seed orchards
Authors: Chaloupková Kateřina , Lstibůrek Milan 
Published: September 2022

Abstract
Key message
We provide a mathematical model to determine which trees should be ruled out from the grid to promote random mating in seed orchards under genetic thinning.

Context
Genetic thinning (roguing) is a common practice in forest tree breeding to remove inferior genotypes in seed orchards, thus boosting the genetic worth of the seed crop.

Aims
To develop a general methodology for spatial optimization of genetic thinning. It should promote random mating and consider any existing seed orchard layout.

Methods
The model is based on the Optimum-Neighborhood Allocation algorithm (Chaloupková et al., Forests 10:1-6, 2019). The algorithm’s efficiency was evaluated using computer simulation. A fully randomized scheme was used as a reference. In addition, the study provides a demonstration on an actual seed orchard.

Results
Simulations confirm the method’s efficiency in promoting random mating compared to the fully randomized allocation across a wide range of selection intensities. We suggest Linear Deployment as a preferred method for calculating optimum deployment contributions at higher thinning intensities. The algorithm was programmed in R and is publicly available.

Conclusion
Breeders can use the software and follow the example to implement genetic thinning in different practical scenarios assuming any seed orchard layout. The approach enhances random mating while maximizing genetic response to selection.
An inverse problem of fourth-order partial differential equation with nonlocal integral condition
Authors: Huntul M. J. , Abbas Muhammad 
Published: September 2022

AbstractIn this study, the time-dependent potential coefficient in a higher-order PDE with initial and boundary conditions is numerically constructed for the first time from a nonlocal integral condition. Even though the inverse identification problem investigated in this study is ill-posed, it has a unique solution. For discretizing the direct problem and finding stable and accurate solutions, we employ the Quintic B-spline (QBS) collocation and Tikhonov regularization methods, respectively. The following nonlinear minimization problem is solved using MATLAB. The collected findings demonstrate that accurate and stable solutions can be found.
ABOT: an open-source online benchmarking tool for machine learning-based artefact detection and removal methods from neuronal signals
Authors: Fabietti Marcos , Mahmud Mufti , Lotfi Ahmad , Kaiser M. Shamim 
Published: September 2022

AbstractBrain signals are recorded using different techniques to aid an accurate understanding of brain function and to treat its disorders. Untargeted internal and external sources contaminate the acquired signals during the recording process. Often termed as artefacts, these contaminations cause serious hindrances in decoding the recorded signals; hence, they must be removed to facilitate unbiased decision-making for a given investigation. Due to the complex and elusive manifestation of artefacts in neuronal signals, computational techniques serve as powerful tools for their detection and removal. Machine learning (ML) based methods have been successfully applied in this task. Due to ML’s popularity, many articles are published every year, making it challenging to find, compare and select the most appropriate method for a given experiment. To this end, this paper presents ABOT (Artefact removal Benchmarking Online Tool) as an online benchmarking tool which allows users to compare existing ML-driven artefact detection and removal methods from the literature. The characteristics and related information about the existing methods have been compiled as a knowledgebase (KB) and presented through a user-friendly interface with interactive plots and tables for users to search it using several criteria. Key characteristics extracted from over 120 articles from the literature have been used in the KB to help compare the specific ML models. To comply with the FAIR (Findable, Accessible, Interoperable and Reusable) principle, the source code and documentation of the toolbox have been made available via an open-access repository.
Effect of risk factors for acneiform rash induced by anti-epidermal growth factor receptor antibody drugs on survival: a retrospective observational study
Authors: Takahashi Hiroaki , Yaegashi Yukiko , Saito Yoko , Nihei Satoru , Tairabune Tomohiko , Ujiie Haruki , Asaka Junichi , Kudo Kenzo 
Published: September 2022

Abstract
Background
We previously reported that high body weight was a risk factor affecting the onset of anti-epidermal growth factor receptor (EGFR) antibody drug-induced acneiform rash. The current study investigated the relationship between risk factors for anti-EGFR antibody drug-induced acneiform rash and survival probability in colorectal cancer patients, as well as effects of drug withdrawal, dose reduction, or treatment discontinuation on treatment continuation.

Methods
This retrospective study included 67 patients with unresectable advanced or recurrent colorectal cancer treated with anti-EGFR antibody drugs for the first time.

Results
The survival time and acneiform rash grade of patients with high body weight (≥ 67.2 kg) were significantly longer and higher than those of patients with low body weight (< 67.2 kg). Moreover, the treatment continuation time of patients with drug withdrawal or dose reduction was significantly longer than that of patients without drug withdrawal or dose reduction or with/without treatment discontinuation. Meanwhile, the treatment continuation time of patients with treatment discontinuation was significantly shorter than that of patients with drug withdrawal or dose reduction or those without drug withdrawal, dose reduction, or treatment discontinuation.

Conclusions
High body weight is a novel prognostic factor for patients receiving cancer drugs with anti-EGFR antibody drugs. Hence, the results of this study suggest that patients with high body weight should be carefully monitored for the development of acneiform rash when receiving anti-EGFR antibody drugs as cancer drug therapy.
Determinants of adolescents’ contraceptive uptake in Ethiopia: a systematic review of literature
Authors: Mekonnen Alemayehu Gonie , Odo Daniel Bogale , Nigatu Dabere , Amare Nakachew Sewnet , Tizazu Michael Amera 
Published: September 2022

Abstract
Introduction
Various studies have identified different factors that affect adolescent contraceptive uptake in different parts of Ethiopia. However, varying results were reported across primary studies and those results need to be systematically collated to inform policies. Therefore, this systematic review aimed to synthesize the findings of those primary studies to obtain more robust and representative evidence about adolescent contraceptive uptake in Ethiopia.

Methods
Five databases (MEDLINE via PubMed, Google Scholar, Scopus, Science Direct and CINAHL) were searched for papers published from January 2000 up to June 2021 in English. We limited our search to start on January 2000 as the health of adolescents have been given more attention after this period and to avoid time-lapsed biases. Seven studies were included in this systematic review. We used the Newcastle-Ottawa Scale and the Mixed Methods Appraisal Tool for quality assessment of the selected studies.

Results
Determinants of adolescent contraceptive utilization were focused on four levels: individual, socio-cultural, healthcare service and knowledge related factors. Individual-related factors that influence adolescents’ contraceptive uptake include; being in the age group of 10–15 years, not currently enrolled in school and being from low-income families, while socio-cultural factors include: lack of discussion with family members, arranged marriage, pressure from a partner, harmful traditional practices, discussion with peer groups and sexual partners. Healthcare service-related factors include; lack of information about contraceptives during health facility visits, lack of privacy during service provision and inconvenient service hours at health facilities, and not visiting health facilities, whereas, knowledge related factors include; having knowledge of contraceptive methods and being heard about contraceptives from media. Also, the proportion of adolescent contraceptive uptake ranged from 12 to 79%.

Conclusions
In this systematic, individual, socio-cultural, health-care-related, and knowledge-related characteristics have all been identified as influencing adolescents’ contraceptive uptake in Ethiopia. Hence, integrated interventions aimed at overcoming barriers to adolescent contraceptive uptake would be beneficial to improving adolescent contraceptive utilization in Ethiopia.
Influence of Pleistocene climate fluctuations on the demographic history and distribution of the critically endangered Chinese pangolin (Manis pentadactyla)
Authors: Wei Shichao , Sun Song , Dou Hongliang , An Fuyu , Gao Haiyang , Guo Ce , Hua Yan 
Published: September 2022

Abstract
Background
Pleistocene climate fluctuations have strongly modified species genetic diversity and distributions. The Chinese pangolin (Manis pentadactyla) has been recognized as a critically endangered animal due to heavy poaching and trafficking. However, the effect of Pleistocene climate fluctuations on the genetic diversity and spatial distribution of the Chinese pangolin remains largely unknown. Here, we combined whole genome sequencing data, analysis of complete mitochondrial genomes, and a large amount of occurrence data from field surveys to infer the ancestral demographic history and predict the past spatial dynamics of the Chinese pangolin in Guangdong Province, China.

Results
Our results indicated that there were two subpopulations, which showed similar trends of population size change in response to past climatic changes. We estimated a peak effective population size (Ne) during the last interglacial (LIG), followed by a marked decrease (~ 0.5 to fivefold change) until the last glacial maximum (LGM) and a rebound to a small peak population size during the Mid-Holocene (MH). The estimated time of the separation event between two subpopulations was approximately 3,000–2,500 years ago (ka). We estimated that the distribution of suitable areas shrank by 14.4% from the LIG to LGM, followed by an expansion of 31.4% from the LGM to MH and has been stable since then. In addition, we identified an elevational shift and suitable area decreased significantly during the LGM, but that the geographic extent of suitable areas in the western region increased from the LIG to present. The eastern region of Guangdong Province had the highest habitat suitability across all the climate scenarios.

Conclusions
Our results suggested that Pleistocene climate fluctuations played an important role in shaping patterns of genetic diversity and spatial distribution, and that human stressors likely contributed to the recent divergence of two Chinese pangolin subpopulations sampled here. We argue that a key protected area should be established in the eastern region of Guangdong Province. As such, this study provides a more thorough understanding of the impacts of Pleistocene climate fluctuations impacts on a mammalian species in southern China and suggests more robust management and conservation plans for this Critically Endangered species of special interest.
Validation of age- and sex-dependent association of uric acid and incident hypertension in rural areas
Authors: Kim In Jae , Kim Woohyeun , Go Tae Hwa , Kang Dae Ryong , Kim Jang-Young , Kim Eung Ju 
Published: September 2022

AbstractBackgroundA previous study based on urban areas suggested the age- and sex-dependent association of uric acid (UA) and incident hypertension. We aimed to investigate whether this association is valid even in rural areas with different lifestyle.MethodsData from the cardiovascular disease association study, a prospective cohort study based on rural residents, was analyzed. A total of 4,592 subjects (mean age, 60.1 ± 9.5 years; men, 37.7%) without hypertension were included. We first investigated whether UA was a risk factor for incident hypertension using Cox regression, and then compared the relative risk by stratification according to age and sex.ResultsDuring the follow-up period (mean, 2.0 years), 579 subjects (12.6%) were newly diagnosed with hypertension. The risk factors for incident hypertension were age (Hazard ratios [HR] for ≥ 65, 1.26), systolic blood pressure (HR per 1 mmHg increase, 1.07), and serum UA concentration (HR per 1 mmHg increase, 1.10). The risk of UA-related incident hypertension was higher in the non-elderly than in the elderly for both men and women (HR, 1.74 for non-elderly men; 1.88 for non-elderly women; 1.66 for elderly men; 1.10 for elderly women). Even after adjusting for multiple confounders, the risk of UA-related incident hypertension was significantly higher in non-elderly women (HR, 1.59;P < 0.05).ConclusionsAge- and sex-dependent association of UA with incident hypertension suggested in cohort study based on urban areas was consistently found in rural areas as well. In particular, non-elderly women were at a higher risk for UA-related incident hypertension.
Technical transfer and commercialisation of lyophilised biopharmaceuticals — application of lyophiliser characterisation and comparability
Authors: Cullen Sean , Walsh Emma , Gervasi Valeria , Khamar Dikshitkumar , McCoy Timothy R. 
Published: September 2022

Abstract
A holistic approach was taken to characterise lyophilisers at both laboratory and commercial scale to design a focused validation strategy for commercialising parenteral drug products. Vial heat transfer coefficients (Kv) and equipment mass transfer boundaries were generated for a Lyostar II and three commercial scale IMA Lyomax lyophilisers. Kv studies were performed using gravimetric methodologies. Kv calculated for the Lyostar II was equivalent to the commercial equipment at 133 µBar however trended higher below 133 µBar and lower above 133 µBar potentially impacting primary drying product temperature during scale-up depending on the chamber pressure recipe set point. Kv profiles were consistent within and across the commercial equipment. Edge effect was most prominent at commercial scale with minimal shielding of the edge vials in contrast to the presence of a metal ring around the vial pack in the Lyostar II. Equipment capability studies for mass transfer showed commercial scale equipment could achieve lower chamber pressure and greater sublimation rates when compared to the Lyostar II. Furthermore, differences were also measured between large-scale lyophilisers based on condenser orientation (horizontal vs vertical). The results demonstrate greater equipment capability of the two-storey vertical configuration with respect to choked flow regime. Worst-case locations within a commercial lyophiliser were identified providing rationale for reduced sampling for product shelf-mapping locations. This work provides guidance on execution of commercial scale characterisation studies and application of the data to enhance scale-up, technical transfer and focused process validation strategies.