bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of changing risk thresholds on the number of people in England eligible for urgent investigation for possible cancer: an observational cross-sectional study
Authors: Moore Sarah F. , Price Sarah J. , Chowienczyk Sarah , Bostock Jennifer , Hamilton Willie 
Published: September 2021

Abstract
Background
Expediting cancer diagnosis may be achieved by targeted decreases in referral thresholds to increase numbers of patients referred for urgent investigation.

Methods
Clinical Practice Research Datalink data from England for 150,921 adults aged ≥40 were used to identify participants with features of possible cancer equating to risk thresholds ≥1%, ≥2% or ≥3% for breast, lung, colorectal, oesophago-gastric, pancreatic, renal, bladder, prostatic, ovarian, endometrial and laryngeal cancers.

Results
The mean age of participants was 60 (SD 13) years, with 73,643 males (49%). In 2016, 8576 consultation records contained coded features having a positive predictive value (PPV) of ≥3% for any of the 11 cancers. This equates to a rate of 5682/100,000 patients compared with 4601/100,000 Suspected Cancer NHS referrals for these cancers from April 2016–March 2017. Nine thousands two hundred ninety-one patient-consultation records had coded features equating to a ≥2% PPV, 8% more than met PPV ≥ 3%. Similarly, 19,517 had features with a PPV ≥ 1%, 136% higher than for PPV ≥ 3%.

Conclusions
This study estimated the number of primary-care patients presenting at lower thresholds of cancer risk. The resource implications of liberalising this threshold to 2% are modest and manageable. The details across individual cancer sites should assist planning of English cancer services.
Insulin-like growth factor binding protein-1 regulates HIF-1α degradation to inhibit apoptosis in hypoxic cardiomyocytes
Authors: Tang Xiaoyan , Jiang Huilin , Lin Peiyi , Zhang Zhenhui , Chen Meiting , Zhang Yi , Mo Junrong , Zhu Yongcheng , Liu Ningning , Chen Xiaohui 
Published: September 2021

AbstractHypoxia is important in ischemic heart disease. Excessive Insulin-like growth factor binding protein-1 (IGFBP-1) amounts are considered to harm cardiomyocytes in acute myocardial infarction. However, the mechanisms by which IGFBP-1 affects cardiomyocytes remain undefined. The present study demonstrated that hypoxia up-regulates IGFBP-1 and HIF-1α protein expression in cardiomyocytes. Subsequent assays showed that IGFBP-1 suppression decreased HIF-1α expression and inhibited hypoxia-induced apoptosis in cardiomyocytes, which was reversed by HIF-1α overexpression, indicating that HIF-1α is essential to IGFBP-1 function in cellular apoptosis. In addition, we showed that IGFBP-1 regulated HIF-1α stabilization through interacting with VHL. The present findings suggest that IGFBP-1–HIF-1α could be targeted for treating ischemic heart disease.
miR-139-5p sponged by LncRNA NEAT1 regulates liver fibrosis via targeting β-catenin/SOX9/TGF-β1 pathway
Authors: Wang Qi , Wei Song , Li Lei , Bu Qingfa , Zhou Haoming , Su Wantong , Liu Zheng , Wang Mingming , Lu Ling 
Published: September 2021

AbstractLiver fibrosis is a patho-physiological process which can develop into cirrhosis, and hepatic carcinoma without intervention. Our study extensively investigated the mechanisms of lncRNA NEAT1 and miR-139-5p in regulating liver fibrosis progression. Our results demonstrated that the expression of lncRNA NEAT1 was increased and the expression of miR-139-5p was decreased in fibrotic liver tissues. LncRNA NEAT1 could sponge miR-139-5p and promoted hepatic stellate cells (HSCs) activation by directly inhibiting the expression of miR-139-5p. The co-localization of lncRNA NEAT1 with miR-139-5p was shown in the cytosols of activated HSCs. miR-139-5p upregulation could suppress the expression of β-catenin. The overexpression of β-catenin promoted HSCs activation. Moreover, we found that β-catenin could interact with SOX9 promoted HSCs activation. Our further studies demonstrated that SOX9 could bind with the TGF-β1 promoter and promoted the transcription activity of TGF-β1. The upregulation of TGF-β1 further promoted HSCs activation. In vivo study also suggested that lncRNA NEAT1 knockdown and miR-139-5p overexpression alleviated murine liver fibrosis. LncRNA NEAT1 exacerbated liver fibrosis by suppressing the expression of miR-139-5p. Collectively, our study suggested that miR-139-5p sponged by lncRNA NEAT1 regulated liver fibrosis via targeting β-catenin/SOX9/TGF-β1 Pathway.
Radiation-induced liver injury and hepatocyte senescence
Authors: Zhu Wei , Zhang Xiaofen , Yu Mengli , Lin Bingru , Yu Chaohui 
Published: September 2021

AbstractRadiation-induced liver injury (RILI) is a major complication of radiotherapy during treatment for liver cancer and other upper abdominal malignant tumors that has poor pharmacological therapeutic options. A series of pathological changes can be induced by radiation. However, the underlying mechanism of RILI remains unclear. Radiation can induce cell damage via direct energy deposition or reactive free radical generation. Cellular senescence can be observed due to the DNA damage response (DDR) caused by radiation. The senescence-associated secretory phenotype (SASP) secreted from senescent cells can cause chronic inflammation and aggravate liver dysfunction for a long time. Oxidative stress further activates the signaling pathway of the inflammatory response and affects cellular metabolism. miRNAs clearly have differential expression after radiation treatment and take part in RILI development. This review aims to systematically profile the overall mechanism of RILI and the effects of radiation on hepatocyte senescence, laying foundations for the development of new therapies.
Effects of intrapolyp steroid injection on intraocular pressure and recurrent polyp treatment
Authors: Lee Tae-Hoon , Nam Jung-Gwon , Lee Chang Kyu 
Published: September 2021

Abstract
Purpose
To examine the effects of intrapolyp triamcinolone acetonide (TA) injections on intraocular pressure (IOP) and recurrence of nasal polyps after endoscopic sinus surgery.

Patients and methods
This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized into either the TA injection group (Group I, 20 mg/ml, 2 mL) or the placebo normal saline injection group (group II, 2 mL). There were a total of five study visits: one baseline visit and one at 2, 4, 8, and 12 w after the injection. The primary safe outcome was the change in IOP between two groups at 4 w. The secondary safe outcome was the IOP at each visit and proportion of patients having IOP above 21 mmHg at 4 and 8 w. Changes in the nasal polyp size were measured between two groups at each visit.

Results
A total of 43 consenting participants completed this study (22 in group I and 21 in group II). The mean IOP elevation in both eyes was not significantly different between the groups (p > 0.05) and was not over 2 mmHg at the 4-w mark. There was also no significant difference in the proportion of patients having IOP above 21 mmHg at 4 and 8 w between the groups (p > 0.05). However, there was a significant difference in the change in polyp size until 8 w between both groups (p < 0.01).

Conclusions
Intrapolyp TA injection is a safe and effective method for the management of recurrent polyps after endoscopic sinus surgery.
Unravelling the therapeutic potential of IL-33 for atrophic AMD
Authors: Clare Alison J. , Liu Jian , Copland David A. , Theodoropoulou Sofia , Dick Andrew D. 
Published: September 2021

AbstractAge-related macular degeneration (AMD), a degenerative disease affecting the retinal pigment epithelium (RPE) and photoreceptors in the macula, is the leading cause of central blindness in the elderly. AMD progresses to advanced stages of the disease, atrophic AMD (aAMD), or in 15% of cases “wet” or neovascular AMD (nAMD), associated with substantial vision loss. Whilst there has been advancement in therapies treating nAMD, to date, there are no licenced effective treatments for the 85% affected by aAMD, with disease managed by changes to diet, vitamin supplements, and regular monitoring. AMD has a complex pathogenesis, involving highly integrated and common age-related disease pathways, including dysregulated complement/inflammation, impaired autophagy, and oxidative stress. The intricacy of AMD pathogenesis makes therapeutic development challenging and identifying a target that combats the converging disease pathways is essential to provide a globally effective treatment. Interleukin-33 is a cytokine, classically known for the proinflammatory role it plays in allergic disease. Recent evidence across degenerative and inflammatory disease conditions reveals a diverse immune-modulatory role for IL-33, with promising therapeutic potential. Here, we will review IL-33 function in disease and discuss the future potential for this homeostatic cytokine in treating AMD.
Acetylcholine prioritises direct synaptic inputs from entorhinal cortex to CA1 by differential modulation of feedforward inhibitory circuits
Authors: Palacios-Filardo Jon , Udakis Matt , Brown Giles A. , Tehan Benjamin G. , Congreve Miles S. , Nathan Pradeep J. , Brown Alastair J. H. , Mellor Jack R. 
Published: September 2021

AbstractAcetylcholine release in the hippocampus plays a central role in the formation of new memory representations. An influential but largely untested theory proposes that memory formation requires acetylcholine to enhance responses in CA1 to new sensory information from entorhinal cortex whilst depressing inputs from previously encoded representations in CA3. Here, we show that excitatory inputs from entorhinal cortex and CA3 are depressed equally by synaptic release of acetylcholine in CA1. However, feedforward inhibition from entorhinal cortex exhibits greater depression than CA3 resulting in a selective enhancement of excitatory-inhibitory balance and CA1 activation by entorhinal inputs. Entorhinal and CA3 pathways engage different feedforward interneuron subpopulations and cholinergic modulation of presynaptic function is mediated differentially by muscarinic M3 and M4 receptors, respectively. Thus, our data support a role and mechanisms for acetylcholine to prioritise novel information inputs to CA1 during memory formation.
Deep learning ferroelectric polarization distributions from STEM data via with and without atom finding
Authors: Nelson Christopher T. , Ghosh Ayana , Oxley Mark , Zhang Xiaohang , Ziatdinov Maxim , Takeuchi Ichiro , Kalinin Sergei V. 
Published: September 2021

AbstractOver the last decade, scanning transmission electron microscopy (STEM) has emerged as a powerful tool for probing atomic structures of complex materials with picometer precision, opening the pathway toward exploring ferroelectric, ferroelastic, and chemical phenomena on the atomic scale. Analyses to date extracting a polarization signal from lattice coupled distortions in STEM imaging rely on discovery of atomic positions from intensity maxima/minima and subsequent calculation of polarization and other order parameter fields from the atomic displacements. Here, we explore the feasibility of polarization mapping directly from the analysis of STEM images using deep convolutional neural networks (DCNNs). In this approach, the DCNN is trained on the labeled part of the image (i.e., for human labelling), and the trained network is subsequently applied to other images. We explore the effects of the choice of the descriptors (centered on atomic columns and grid-based), the effects of observational bias, and whether the network trained on one composition can be applied to a different one. This analysis demonstrates the tremendous potential of the DCNN for the analysis of high-resolution STEM imaging and spectral data and highlights the associated limitations.
Minimal-active-space multistate density functional theory for excitation energy involving local and charge transfer states
Authors: Zhao Ruoqi , Hettich Christian P. , Chen Xin , Gao Jiali 
Published: September 2021

AbstractMultistate density functional theory (MSDFT) employing a minimum active space (MAS) is presented to determine charge transfer (CT) and local excited states of bimolecular complexes. MSDFT is a hybrid wave function theory (WFT) and density functional theory, in which dynamic correlation is first incorporated in individual determinant configurations using a Kohn–Sham exchange-correlation functional. Then, nonorthogonal configuration-state interaction is performed to treat static correlation. Because molecular orbitals are optimized separately for each determinant by including Kohn–Sham dynamic correlation, a minimal number of configurations in the active space, essential to representing low-lying excited and CT states of interest, is sufficient to yield the adiabatic states. We found that the present MAS-MSDFT method provides a good description of covalent and CT excited states in comparison with experiments and high-level computational results. Because of the simplicity and interpretive capability through diabatic configuration weights, the method may be useful in dynamic simulations of CT and nonadiabatic processes.
Yield of clinically reportable genetic variants in unselected cerebral palsy by whole genome sequencing
Authors: van Eyk C. L. , Webber D. L. , Minoche A. E. , Pérez-Jurado L. A. , Corbett M. A. , Gardner A. E. , Berry J. G. , Harper K. , MacLennan A. H. , Gecz J. 
Published: September 2021

AbstractCerebral palsy (CP) is the most common cause of childhood physical disability, with incidence between 1/500 and 1/700 births in the developed world. Despite increasing evidence for a major contribution of genetics to CP aetiology, genetic testing is currently not performed systematically. We assessed the diagnostic rate of genome sequencing (GS) in a clinically unselected cohort of 150 singleton CP patients, with CP confirmed at >4 years of age. Clinical grade GS was performed on the proband and variants were filtered, and classified according to American College of Medical Genetics and Genomics–Association for Molecular Pathology (ACMG-AMP) guidelines. Variants classified as pathogenic or likely pathogenic (P/LP) were further assessed for their contribution to CP. In total, 24.7% of individuals carried a P/LP variant(s) causing or increasing risk of CP, with 4.7% resolved by copy number variant analysis and 20% carrying single nucleotide or indel variants. A further 34.7% carried one or more rare, high impact variants of uncertain significance (VUS) in variation intolerant genes. Variants were identified in a heterogeneous group of genes, including genes associated with hereditary spastic paraplegia, clotting and thrombophilic disorders, small vessel disease, and other neurodevelopmental disorders. Approximately 1/2 of individuals were classified as likely to benefit from changed clinical management as a result of genetic findings. In addition, no significant association between genetic findings and clinical factors was detectable in this cohort, suggesting that systematic sequencing of CP will be required to avoid missed diagnoses.
Analyzing climate change impacts on health, energy, water resources, and biodiversity sectors for effective climate change policy in South Korea
Authors: Moon Tae Hoon , Chae Yeora , Lee Dong-Sung , Kim Dong-Hwan , Kim Hyun-gyu 
Published: September 2021

AbstractThis study analyzes how climate change affects the economy, society, and environment in South Korea. Then, the study explores the ways to strengthen capabilities that can alleviate climate change impacts. To find them, the study employs a system dynamics simulation method and builds a model with several sectors including the urban, rural, population, and social-environmental sectors. The study compares the size of climate change damages in rural and urban areas. The results with representative concentration path (RCP) 8.5 show that the size of climate change damage will continue to increase by 2050. The projected damages from the reduced industrial outputs in urban areas will be larger than that in rural areas. The results also show that the service sector will face stronger impacts from climate change than the manufacturing and agricultural sectors. However, the total size of damage in the rural areas will be bigger than that of the urban areas. It is because the size of reduced industrial outputs per capita in the rural areas is twice bigger than that of the urban areas. The climate change damage in the social and environmental sectors (including a loss of biodiversity and an increase in health costs) account for the largest part of the total damage. The study finally provides suggestions and policies that can improve the capabilities to reduce the climate change damages. One of the major suggestions of this study is that the increase in the climate change budget corresponding to the GDP growth can minimize the size of climate change impacts.
Cell polarity and cell adhesion associated gene expression differences between invasive micropapillary and no special type breast carcinomas and their prognostic significance
Authors: Kramer Zsófia , Kenessey István , Gángó Ambrus , Lendvai Gábor , Kulka Janina , Tőkés Anna-Mária 
Published: September 2021

AbstractInvasive micropapillary carcinoma of the breast (IMPC) has been in the focus of several studies given its specific histology and clinicopathological course. We analysed mRNA expression profiles and the prognostic value of 43 genes involved in cell polarity, cell-adhesion and epithelial–mesenchymal transition (EMT) in IMPC tumors and compared them to invasive breast carcinomas of no special type (IBC-NST). IMPCs (36 cases), IBC-NSTs (36 cases) and mixed IMPC-IBC NSTs (8 cases) were investigated. mRNA expression level of selected genes were analysed using the NanoString nCounter Analysis System. Distant metastases free survival (DMFS) intervals were determined. Statistical analysis was performed using Statistica 13.5 software. Twelve genes showed significantly different expression in the IMPC group. There was no difference in DMFS according to histological type (IBC-NST vs. IMPC). High CLDN3, PALS1 and low PAR6 expression levels in the entire cohort were associated with shorter DMFS, and PALS1 was proven to be grade independent prognostic factor. Positive lymph node status was associated with higher levels of AKT1 expression. Differences in gene expression in IMPC versus IBC-NST may contribute to the unique histological appearance of IMPCs. No marked differences were observed in DMFS of the two groups. Altered gene expression in the mTOR signaling pathway in both tumor subtypes highlights the potential benefit from AKT/mTOR inhibitors in IMPCs similarly to IBC-NSTs.
The noncoding RNA LINC00152 conveys contradicting effects in different glioblastoma cells
Authors: Binder Stefanie , Zipfel Ivonne , Müller Claudia , Wiedemann Karolin , Schimmelpfennig Carolin , Pfeifer Gabriele , Reiche Kristin , Hauschildt Sunna , Lehmann Jörg , Köhl Ulrike , Horn Friedemann , Friedrich Maik 
Published: September 2021

AbstractGlioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by its high genetic heterogeneity. In search of novel putative therapeutic RNA targets we investigated the role of the oncogenic long noncoding RNA LINC00152 (CYTOR, and STAiR18) in A172 glioblastoma cells. Here, we are the first to describe, that LINC00152 unexpectedly acts in a tumor suppressive manner in this cell line. SiRNA-based knockdown of LINC00152 enhanced malignant tumor behaviors including proliferation, cell cycle entry, migration, and invasion, contradicting previous studies using U87-MG and LN229 glioblastoma cells. Furthermore, LINC00152 knockdown had no influence on survival of A172 glioblastoma cells. In a genome wide transcription analysis of A172 and U87-MG glioblastoma cells, we identified 70 LINC00152 target genes involved in locomotion, cell migration, and motility in A172 cells, whereas in U87-MG cells only 40 target genes were detected. The LINC00152-regulated genes found in A172 differed from those identified in U87-MG glioblastoma cells, none of them being regulated in both cell lines. These findings underline the strong genetic heterogeneity of glioblastoma and point to a potential, yet unknown risk addressing LINC00152 lncRNA as a prospective therapeutic target in GBM.
Antitumorigenic effect of insect-derived peptide poecilocorisin-1 in human skin cancer cells through regulation of Sp1 transcription factor
Authors: Lee Ra Ham , Oh Jae-Don , Hwang Jae Sam , Lee Hak-Kyo , Shin Donghyun 
Published: September 2021

AbstractMalignant melanoma is highly resistant to conventional treatments and is one of the most aggressive types of skin cancers. Conventional cancer treatments are limited due to drug resistance, tumor selectivity, and solubility. Therefore, new treatments with fewer side effects and excellent effects should be developed. In previous studies, we have analyzed antimicrobial peptides (AMPs), which showed antibacterial and anti-inflammatory effects in insects, and some AMPs also exhibited anticancer efficacy. Anticancer peptides (ACPs) are known to have fewer side effects and high anticancer efficacy. In this study, the insect-derived peptide poecilocorisin-1 (PCC-1) did not induce toxicity in the human epithelial cell line HaCaT, but its potential as an anticancer agent was confirmed through specific effects of antiproliferation, apoptosis, and cell cycle arrest in two melanoma cell lines, SK-MEL-28 and G361. Additionally, we discovered a novel anticancer mechanism of insect-derived peptides in melanoma through the regulation of transcription factor Sp1 protein, which is overexpressed in cancer, apoptosis, and cell cycle-related proteins. Taken together, this study aims to clarify the anticancer efficacy and safety of insect-derived peptides and to present their potential as future therapeutic agents.
A nationwide study of patients with monoclonal gammopathy of undetermined significance with a 10-year follow-up in South Korea
Authors: Kang Ka-Won , Song Ji Eun , Lee Byung-Hyun , Jeon Min Ji , Yu Eun Sang , Kim Dae Sik , Lee Se Ryeon , Sung Hwa Jung , Choi Chul Won , Park Yong , Kim Byung Soo 
Published: September 2021

AbstractIn clinical practice, most patients with monoclonal gammopathy of undetermined significance (MGUS) undergo long-term follow-up without disease progression. There is insufficient real-world data about how closely and whether anything other than disease progression should be monitored. Herein, we performed a nationwide study of 470 patients with MGUS with a 10-year follow-up to determine the patterns of disease progression and other comorbidities. During the follow-up period, 158 of 470 patients with MGUS (33.62%) progressed to symptomatic monoclonal gammopathies. Most of these were multiple myeloma (134/470 patients, 28.51%), and those diagnosed within 2 years after diagnosis of MGUS was high. Approximately 30–50% of patients with MGUS had hypertension, diabetes, hyperlipidemia, and osteoarthritis at the time of diagnosis, and these comorbidities were newly developed during the follow-up period in approximately 50% of the remaining patients with MGUS. Approximately 20–40% of patients with MGUS have acute or chronic kidney failure, thyroid disorders, disc disorders, peripheral neuropathy, myocardial infarction, stroke, and heart failure during the follow-up period. Altogether, when MGUS is diagnosed, close follow-up of the possibility of progression to multiple myeloma is required, especially within 2 years after diagnosis; simultaneously, various comorbidities should be considered and monitored during the follow-up of patients with MGUS. Continuous research is needed to establish appropriate follow-up guidelines.