bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal trends in the incidence of malignant and nonmalignant primary brain and central nervous system tumors by the method of diagnosis in England, 1993–2017
Authors: Ali Usama M , Withrow Diana R , Judge Andrew D , Plaha Puneet , Darby Sarah C 
Published: January 2023

Abstract

Background
Several studies report increases in the incidences of primary central nervous system (CNS) tumors. The reasons for this are unclear.

Methods
Data on all 188 340 individuals diagnosed with a primary CNS tumor in England (1993–2017) were obtained from the National Cancer Registration and Analysis Service. Data on all computerized tomography (CT) head and magnetic resonance imaging (MRI) brain scans in England (2013–2017) were obtained from the National Health Service Digital. Age-sex-standardized annual incidence rates per 100 000 population (ASR) were calculated by calendar year, tumor behavior, tumor location, and method of diagnosis. Temporal trends were quantified using average annual percent change (AAPC).

Results
The ASR for all CNS tumors increased from 13.0 in 1993 to 18.6 in 2017 (AAPC: +1.5%, 95% CI: 1.3, 1.7). The ASR for malignant tumors (52% overall) remained stable (AAPC: +0.5%, 95% CI: −0.2, 1.3), while benign tumors (37% overall) increased (AAPC: +2.6%, 95% CI: 1.2, 4.0). Among the 66% of benign tumors that were microscopically confirmed, the ASR increased modestly (AAPC: +1.3%, 95% CI: 0.5, 2.1). However, among the 25% of benign tumors that were radiographically confirmed, the ASR increased substantially (AAPC: 10.2%, 95% CI: 7.9, 12.5), principally driven by large increases in those who are aged 65+ years. The rate of CT head scans in Accident & Emergency (A&E) increased during 2013–2017, with especially large increases in 65–84 and 85+-year-olds (AAPCs: +18.4% and +22.5%).

Conclusions
Increases in CNS tumor incidence in England are largely attributable to the greater detection of benign tumors. This could be the result of the increasing use of neuroimaging, particularly CT head scans in A&E in people who are aged 65+ years.
Cell Cycle Dynamics during Stomatal Development: Window of MUTE Action and Ramification of Its Loss-of-Function on an Uncommitted Precursor
Authors: Zuch Daniel T , Herrmann Arvid , Kim Eun-Deok , Torii Keiko U 
Published: January 2023

AbstractPlants develop in the absence of cell migration. As such, cell division and differentiation need to be coordinated for functional tissue formation. Cellular valves on the plant epidermis, stomata, are generated through a stereotypical sequence of cell division and differentiation events. In Arabidopsis, three master regulatory transcription factors, SPEECHLESS (SPCH), MUTE and FAMA, sequentially drive initiation, proliferation and differentiation of stomata. Among them, MUTE switches the cell cycle mode from proliferative asymmetric division to terminal symmetric division and orchestrates the execution of the single symmetric division event. However, it remains unclear to what extent MUTE regulates the expression of cell cycle genes through the symmetric division and whether MUTE accumulation itself is gated by the cell cycle. Here, we show that MUTE directly upregulates the expression of cell cycle components throughout the terminal cell cycle phases of a stomatal precursor, not only core cell cycle engines but also check-point regulators. Time-lapse live imaging using the multicolor Plant Cell Cycle Indicator revealed that MUTE accumulates up to the early G2 phase, whereas its successor and direct target, FAMA, accumulate at late G2 through terminal mitosis. In the absence of MUTE, meristemoids fail to differentiate and their G1 phase elongates as they reiterate asymmetric divisions. Together, our work provides the framework of cell cycle and master regulatory transcription factors to coordinate a single symmetric cell division and suggests a mechanism for the eventual cell cycle arrest of an uncommitted stem-cell-like precursor at the G1 phase.
ALKBH5 ALLEVIATES HYPOXIA POSTCONDITIONING INJURY IN d-GALACTOSE–INDUCED SENESCENT CARDIOMYOCYTES BY REGULATING STAT3
Authors: Zhang Xuan , Li Feixiang , Ma Ji , Zhang Xiaobei , Yin Yiqing 
Published: January 2023

ABSTRACT
Ischemic postconditioning (I/Post) reduces I/R injury by activating endogenous cardioprotection mechanisms, such as the JAK/signal transducer and activator of transcription 3 (STAT3) and PI3K/Akt pathways, which offer a traditional approach to myocardial protection. According to a previous study, cardioprotection by I/Post may be lost in aged mice, and in our previous research, hypoxic postconditioning (H/Post) lacked a protective effect in senescent cardiomyocytes, which was associated with low expression of long noncoding RNA H19. The N6-methyladenosine (m6A) modification is a dynamic and reversible process that has been confirmed to play a role in cardiovascular diseases. However, the mechanisms of m6A modification in myocardial I/Post remain to be explored. Neonatal cardiomyocytes were isolated from 2-day-old Sprague-Dawley rats, and senescence was induced by d-galactose, followed by stimulation of hypoxia-reoxygenation and H/Post. Hypoxic injury was evaluated by cell viability and the Bcl-2/Bax protein ratio. Total m6A levels were measured using a colorimetric m6A RNA Methylation Quantification Kit, and the m6A modified and differentially expressed mRNA was determined by MeRIP (methylated RNA immunoprecipitation). We found that H/Post increased m6A methylation and decreased RNA mA demethylase alkB homolog 5 (ALKBH5) expression in aged cardiomyocytes. Furthermore, ALKBH5 knockdown exacerbated injury following H/Post in senescent cardiomyocytes. In addition, ALKBH5 regulated STAT3 expression by mediating its m6A modification and long noncoding RNA H19/miR-124-3p. ALKBH5 also alleviated the H/Post injury induced by the low expression of STAT3 in senescent cardiomyocytes.
CircNRIP1 KNOCKDOWN ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED HUMAN KIDNEY 2 CELL APOPTOSIS AND INFLAMMATION THROUGH miR-339-5p/OXSR1 PATHWAY
Authors: Li Pei , Liu Yu , You Ting 
Published: January 2023

ABSTRACT

Background: CircRNA regulates sepsis-induced acute kidney injury (AKI). CircNRIP1 is overexpressed in the blood of AKI patients, but its role in septic AKI occurrence remains unknown. Methods: Human kidney 2 (HK2) cells were stimulated using lipopolysaccharide (LPS) to generate a septic AKI cell model. The expression levels of circNRIP1, miR-339-5p, oxidative stress-responsive kinase 1 (OXSR1), B-cell lymphoma-2 (Bcl2), BCL2-associated x protein (Bax), and cleaved-caspase 3 were detected by quantitative real-time polymerase chain reaction or Western blotting analysis. Cell viability and apoptosis were investigated by cell counting kit-8 and flow cytometry analysis. The release of proinflammatory cytokines was monitored using commercial kits. The associations among circNRIP1, miR-339-5p, and OXSR1 were identified by mechanism assays. Results: CircNRIP1 was dramatically upregulated in the blood of septic AKI patients and LPS-induced HK2 cells. CircNRIP1 depletion protected HK2 cells from LPS-induced apoptosis and inflammation. MiR-339-5p expression was downregulated in the blood of septic AKI patients, and miR-339-5p combined with circNRIP1. Moreover, circNRIP1 knockdown-induced effects involved the upregulation of miR-339-5p in LPS-treated HK2 cells. Comparatively, OXSR1 expression was increased in the blood of septic AKI patients. MiR-339-5p bound to OXSR1, and circNRIP1 modulated OXSR1 expression by interacting with miR-339-5p. Further, ectopic expression of OXSR1 relieved circNRIP1 knockdown-mediated effects in LPS-induced HK2 cells. Conclusion: CircNRIP1 depletion ameliorated LPS-induced HK2 cell damage by regulating the miR-339-5p/OXSR1 pathway.
Linear contraction of stress fibers generates cell body rotation
Authors: Okimura Chika , Akiyama Syu , Nishigami Yukinori , Zaitsu Ryota , Sakurai Tatsunari , Iwadate Yoshiaki 
Published: January 2023

AbstractWounds are healed by crawling migration of the epidermal cells around the injured area. Fish epidermal keratocytes that rapidly repair wounds comprise a frontal crescent-shaped lamellipodium and a rear rugby ball-shaped cell body. The cell body rotates like a wheel during migration. Stress fibers, which are bundles of contractile actomyosin filaments, are arranged along the seams of the rugby ball. Here we show the linear contraction of stress fibers to be the driving force for rotation. We constructed a mechanical model of the cell body that consisted of a soft cylinder with a contractile coil. From the motion of the model, it was predicted that contraction of the stress fibers would deform the soft cell body, as a result of which the deformed cell body would push against the substrate to generate torque. This prediction was confirmed by the observation of stress fiber dynamics in migrating cells. Linear-to-rotation conversion in migrating keratocytes is realized by simple soft-body mechanics. Conversion from linear motion to rotation is widely used in machines with moving parts, but requires somewhat complicated mechanics. An understanding of linear-to-rotation conversion in keratocytes has potential for use in the design of biomimetic soft robots.
Conformational changes in the AdeB transmembrane efflux pump by amphiphilic peptide Mastoparan-B, down-regulates expression of theadeB Gene and restores antibiotics Susceptibility
Authors: Shakibaie Mohammad Reza , Modaresi Farzan , Azizi Omid , Tadjrobehkar Omid , Ghaemi Mohammad Mehdi 
Published: January 2023

ABSTRACTNo report exists on the role of Mastoparan B (MP-B) as an RND efflux pump inhibitor in multi-drug resistant (MDR)Acinetobacter baumannii. Here, we performed a series of in-silico experiments to predict the inhibition of the AdeB efflux pump by MP-B as a drug target agent. For this reason, an MDR strain ofA. baumanniiwas subjected to MICs against 12 antibiotics as well as MP-B. Expression of the adeB gene in the presence and absence of sub-MIC of MP-B was studied by qRT-PCR. It was found that MP-B had potent antimicrobial activity (MIC=1 μg/ml) associated with a 20-fold decrease in theadeB gene expression at the sub-MIC level. The stereochemical analysis using several automated servers confirmed that the AdeB protein is an inner membrane of the RND tripartite complex system with helix-turn-helix conformation and a pore rich in Phe, Ala, and Lys residue. Furthermore, 20 ligands were generated from the initial docked poses to create the correct protein-peptide complexes using the BioLiP pipeline. The pose showed high Z=1.2, C=1.41, TM=0.99, and RMSD=4.4 scores was selected for docking purposes. The molecular docking via AutoDock/Vina revealed that MP-B form H-bound with Val 499, Phe 454, Thr 474, Ser 461, Gly 465, and Tyr 468 residues of the AdeB helix-5 and caused a shift in the dihedral angle (Φ/Ψ) by distances of 9.0 Å, 9.3 Å, and 9.6 Å, respectively. This shift in folding was detected by AlphaFold 2 and influenced the overall druggability of the protein. From the above results, we concluded that MP-B can be a good candidate for bacterial efflux pump inhibition.
PATCRdb: Database of TCRs from data mining patent documents
Authors: Lee Yoona , Freitag Rebecca , Ganesan Rajkumar , Schwämmle Veit , Kumar Sandeep , Krawczyk Konrad 
Published: January 2023

AbstractT-cells are crucial actuators of the innate immune system. Because their receptors recognize intracellular disease markers, there is considerable interest in developing them as novel biotherapies. Computational methods to support discovery, design and development of TCR-based therapeutics need robust repositories of curated sequence and structural information on TCRs. The urgency of this need is highlighted by the recent approval of the first TCR biotherapeutic, tebentafusp. In this work, we have collected patent data on TCR sequences to provide early access to TCRs that are in various stages of product and clinical development (pre-FDA approvals) and are already past the initial discovery / proof of concept (scientific publications) stages. We employ literature mining to identify patent documents disclosing TCR sequences. Such documents are further analyzed to provide a birds-eye view of TCR patenting landscape. We compile the information into a database available athttp://github.com/konradkrawczyk/patcrdbthat we hope should help TCR engineers.
Diagnosis of protozoa diarrhoea inCampylobacterpatients increases markedly with molecular techniques
Authors: Hayman David T S , Garcia-Ramirez Juan Carlos , Pita Anthony , Velathanthiri Niluka , Knox Matthew A , Ogbuigwe Paul , Baker Michael G , Rostami Kamran , Deroles-Main Jan , Gilpin Brent J. 
Published: January 2023

AbstractBackgroundCryptosporidiumandGiardiaare major food and water-borne causes of diarrhoea globally, and two of the most notified infectious diseases in New Zealand. Diagnosis requires laboratory confirmation carried out mostly via antigen or microscopy-based techniques. However, these methods are increasingly being superseded by molecular techniques for diagnostics. Here we investigate the level of protozoa coinfection identified by molecular methods inCampylobacterpositive samples missed through use of antigen-based assays and then investigated different molecular testing protocols.MethodsWe report the findings of two observational studies; the first among 111 people with diarrhoea during a largeCampylobacteroutbreak in Havelock North, and the second a study during normal surveillance activities among 158 people presenting with diarrhoea and a positiveCampylobactertest, but negativeCryptosporidiumand/orGiardiaantigen-based diagnostic test result. The molecular methods used for comparison with the antigen-based tests were in-house end-point PCR tests targeting thegp60gene forCryptosporidiumandgdhgene forGiardia. DNA extraction was performed with and without bead-beating and comparisons with commercial real-time quantitative (qPCR) were made using clinical samples diluted down to 10−5forCryptosporidiumpositive samples.ResultsThe coinfection prevalence was 9% (n= 10, 3–15% 95%CI) forCryptosporidiumand 21% (n=23, 12– 29% 95%CI) forGiardiain the 111Campylobacterpatients of the Havelock North outbreak. The coinfection prevalence was 40% (n=62, 32-48% 95%CI) forCryptosporidiumand 1.3% (n=2, 0.2-4.5% 95%CI) forGiardiain the 158 routine surveillance samples. Sequencing identifiedCryptosporidium hominis, C. parvum, andGiardia intestinalisassemblages A and B among patients. We found no statistical difference in positive test results between samples using end-point PCR with or without bead-beating prior to DNA extraction, or between the in-house end-point PCR and qPCR. The qPCR Ct value was 36 (35-37 95%CI) for 1 oocyst, suggesting a high limit of detection.DiscussionIn surveillance and outbreak situations we found diagnostic serology testing substantially underdiagnosesCryptosporidiumandGiardiacoinfections inCampylobacterpatients. These findings suggest that the impact of protozoa infections may be underestimated, through underdiagnosis, but molecular techniques likely improve detection capabilities. Laboratories need to understand clinical, rather than analytical, test sensitivity, to allow clinicians to better understand the disease aetiologies of patients that enable better health advice.
Spatiotemporal and meteorological trends in dengue transmission in the Dominican Republic, 2015-2019
Authors: Robert Michael A. , Rodrigues Helena Sofia , Herrera Demian , de Mata Donado Campos Juan , Morilla Fernando , Águila Mejía Javier Del , Elena Guardado María , Skewes Ronald , Colomé-Hidalgo Manuel 
Published: January 2023

AbstractDengue has broadened its global distribution substantially in the past two decades, and many endemic areas are experiencing increases in incidence. The Dominican Republic recently experienced its two largest outbreaks to date with 16,836 reported cases in 2015 and 20,123 reported cases in 2019. With this upward trend in dengue transmission, developing tools to better prepare healthcare systems and mosquito control agencies is of critical importance. Before such tools can be developed, however, we must first better understand potential drivers of dengue transmission. To that end, we focus in this paper on determining trends between climate variables and dengue transmission with an emphasis on eight provinces and the capital city of the Dominican Republic in the period 2015-2019. We present summary statistics for dengue cases, temperature, precipitation, and relative humidity in this period, and we conduct an analysis of correlated lags between climate variables and dengue cases as well as correlated lags among dengue cases in each of the nine locations. We find that the southwestern province of Barahona had the largest dengue incidence in both 2015 and 2019. Among all climate variables considered, lags between temperature variables and dengue cases were the most highly correlated. We found that most locations had significant correlations at lags of zero weeks; however, both Barahona and the northern province of Monte Cristi had significantly correlated lags with other provinces at up to eight weeks. These results can be used to improve predictive models of dengue transmission in the country.
Visual field evaluation using Zippy Adaptive Threshold Algorithm (ZATA) Standard and ZATA Fast in patients with glaucoma and healthy individuals
Authors: Nasim Pinaz , Ramesh S Ve , Kuzhuppilly Neetha IR , Naik Preethi , Artes Paul H , Ballae Ganeshrao Shonraj 
Published: January 2023

AbstractPurposeTo evaluate visual fields using Zippy Adaptive Thresholding Algorithm (ZATA) Standard and ZATA Fast among patients with glaucoma and healthy individuals.MethodsWe recruited 22 healthy participants and 55 patients with glaucoma from the ophthalmology clinics at Kasturba Hospital, Manipal, India. Inclusion criteria were age 35 to 85 years, best corrected visual acuity (BCVA) 0.3 logMAR or better. Glaucoma patients had characteristic glaucomatous optic disc damage. All participants were free from any other ocular pathology except from mild cataract. Participants performed ZATA Standard and ZATA Fast tests on a Henson 9000 perimeter and Swedish Interactive Thresholding Algorithm (SITA) Standard and SITA Fast tests on a Humphrey Field Analyser. Tests were repeated within 90 days to evaluate the test-retest variability.ResultsThe mean difference in the mean deviation (MD) values of ZATA Standard and SITA Standard tests was 1.7 dB, and that in ZATA Fast and SITA Fast tests was 0.9 dB. The sensitivity values of ZATA and SITA tests differed by 3 dB. ZATA Standard and ZATA Fast were 30% and 6% faster than the corresponding SITA tests. Grayscale and probability maps varied slightly between the four tests but represented a similar visual field for most patients in the study.ConclusionsZATA Standard and ZATA Fast are suitable for clinical practice. However, differences between ZATA and SITA tests suggest that they should not be used interchangeably when monitoring over time.
Immunomorphogenesis in degenerative disc disease: the role of proinflammatory cytokines and angiogenesis factors
Authors: Pravdyuk N.G. , Novikova A.V. , Shostak N.A. , Buianova A.A. , Patsap O.I. , Raksha A.P. , Timofeyev V.T. , Feniksov V.M. , Nikolayev D.A. , Senko I.V. 
Published: January 2023

ABSTRACTBack pain (BP) due to degenerative spinal injury is a severe, often disabling disease and it tends to decrease age of onset. The cellular and molecular basis of the disc and adjacent structures degradation remains in the focus of pathophysiologists and pathomorphologists close attention. The aim of the study was to determine the expression level of proinflammatory cytokines (IL-1β, IL-6, IL-17) and angiogenesis markers (VEGF-A and CD31) in intervertebral disc (IVD) tissue, their association between each other and between disc degeneration in young people with discogenic BP. In patients who underwent discectomy for a disc herniation, a clinical examination, magnetic resonance imaging (MRI) of the lumbar spine, histological and immunohistochemical analyses of these factors in the disc tissue were performed in comparison with the parameters of healthy group samples (controls). Histology image analysis of IVD fragments of the degenerative disc disease (DDD) group detected zones of inflammatory infiltration, combined with vascularization, the presence of granulation tissue and clusters of chondrocytes in the tissue of nucleus pulposus (NP). Statistically significant expression of IL-1β, IL-6, IL-17 and VEGF-A (especially on the chondrocytes surface) and CD31 (in the disc matrix) was evident in the samples of the DDD group compared with the controls (p < 0.0001), that showed a strong correlation with the histological disc degeneration stage (r > 0.5; p < 0.0001). This denotes a high immunoinflammatory potential of chondrocytes and demonstrates their altered morphogenetic properties. The coincidence of the spatial expression of IL-1β and IL-17 in the perivascular zone endothelium and in the vascular lumen (p < 0.01) was found, which point at the inflammatory synergy of these cytokines. High expression of VEGF-A prevailed on the surface of chondrocytes in cell clusters compared to the matrix (p < 0.0001), indicating that the NP cells trigger the angiogenesis. The absence of CD31 in the cracks of NP with high expression in the disc matrix states the secondary nature of IVD defects due to degeneration, and not due to vascular ingrowth. A high number of patients with Modic changes according to MRI data shown the contribution of cytokines to the formation of reactive spondylitis and the clinical course of BP. These results obtained will help to development molecular/cellular targets and basic strategies for therapy of BP with DDD in the early stages in young people.
A single-cell atlas depicting the cellular and molecular features in human ligamental degeneration: a single cell combined spatial transcriptomics study
Authors: Yang Runze , Xu Tianhao , Zhang Lei , Ge Minghao , Yan Liwei , Li Jian , Fu Weili 
Published: January 2023

AbstractBackgroundTo systematically identify cell types in human ligament, investigate how ligamental cell identities, functions, and interactions participated the process of ligamental degeneration and explore the changes of ligamental microenvironment homeostasis in the disease progression.MethodsUsing single-cell RNA sequencing and spatial RNA sequencing of approximately 49356 cells, we created a comprehensive cell atlas of healthy and degenerated human anterior cruciate ligaments. We explored the variations of the cell subtypes’ spatial distributions and the different processes involved in the disease progression, linked them with ligamental degeneration process using computational analysis.ResultsWe identified new fibroblast subgroups contributed to the disease and mapped out their spatial distribution in the tissue and revealed two stages of the degenerative process. We compared the cellular interactions between different tissue states and identified important signaling pathways may contribute to the disease.ConclusionThis cell atlas provides the molecular foundation for investigating how ligamental cell identities, biochemical functions, and interactions contributed to the ligamental degeneration process. The discoveries revealed the pathogenesis of ligamental degeneration at single-cell and spatial level which is characterized by extracellular matrix remodeling. Our results provide new insights into the control of ligamental degeneration and potential clues to developing novel diagnostic and therapeutic strategies.FundingThis study was funded by the National Natural Science Foundation of China (81972123, 82172508), Sichuan Science and Technology Program (2020YFH0075), Fundamental Research Funds for the Central Universities (2015SCU04A40), Chengdu Science and Technology Bureau Project (2019-YF05-00090-SN), and 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301).