bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-risk Human Papillomavirus 16/18 in oral mucosa and cervix of sexually active women: A comparative pilot study using conventional nested PCR and an in house real-time PCR
Authors: Ramesh Pushkal Sinduvadi , Vyas Rahul , Satishchandra Ruthvik , Arun Brunda , Suma K B , Nataraj Suma M , Shetty Avinash , Shetty Veena , Devegowda Devananda 
Published: March 2022

Abstract
Background: Human papillomavirus (HPV) is known to be associated with both cervical and oropharyngeal cancers, yet little are known about the co-occurrence of similar HPV subtypes in these subsites. With the changing sexual behaviour it is necessary to evaluate the risk of a woman with abnormal cervix developing cancer of the oropharynx. A study evaluating HPV infection in both oral mucosa and the cervix is therefore needed to understand the co-occurrence of HPV infection in 2 different sites. Methods: Oral mucosa and cervical wash specimens were collected from a total of 100 women aged 20-60 years who visited for routine Pap test. DNA was extracted and then subjected to an in house real-time PCR and conventional nested PCR for the detection high risk HPV 16/18 subtypes. A limit of detection was established using serially diluted HPV positive DNA from cell lines and the sensitivity and specificity of both the assays were evaluated. Results: The prevalence of HPV-16/18 in the cervical samples (19.7% vs 6.2%) and the oral mucosa (16.6% vs nil) were higher as detected by our in house real-time PCR in comparison to the conventional nested PCR. Oral HPV infection was found in 25% of the women with SCC of the cervix. Conclusion: Due to the changing sexual behaviour there is a possibility that women with HPV-related cervical lesions can easily transfer the virus to the partner or even self-inoculate which might lead to the development of lesions in the head & neck turning into cancer.
Dichotomine B attenuates neuroinflammatory responses via regulating TLR4/MyD88-mTOR signaling pathway in BV2 cells
Authors: Zhou Xirong , Quan Hongfeng , Zang Lingling , Dong Lin 
Published: March 2022

Abstract
Dichotomine B is a β-Carboline alkaloid isolated from Stellariae Radix. Stellariae Radix is a common Chinese medicine in clinical practice. This herb has been proved to have anti-inflammatory activity. The aim of this study was to investigate the effects and mechanisms of Dichotomine B on neuroinflammation by BV2 microglia induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). The experiment was divided into control group, model group (10 µg/mL LPS + 5mM ATP), model + TLR4 inhibitor (TAK-242, 10 µmol/L) group, model + Dichotomine B (20, 40 and 80 µmol/L) groups and Dichotomine B (80 µmol/L) group. The BV2 cell viability was detected by MTT assay, the morphology of BV2 cells was observed by inverted microscope, the levels of IL-6, IL-1β and TNF-α in BV2 cells were determined by ELISA. The expression levels of TLR4, MyD88, p-mTOR/mTOR, p62, p-RPS6/RPS6, LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins were detected by western blot assay. The expression levels of TLR4, MyD88, mTOR, p62, RPS6, LC3B and Beclin-1 mRNA were detected by PCR assay. Finally, the molecular docking was performed to predict the affinity of Dichotomine B with TLR4, MyD88 and mTOR by LibDock of Discovery Studio. The results showed that compared with the model group, the survival rates of damaged cells were significantly increased by TAK-242 and Dichotomine B, and the morphology of these BV2 cells improved. The levels of IL-6, IL-1β and TNF-α were significantly decreased by TAK-242 and Dichotomine B in LPS/ATP-induced BV2 cells. 80 µmol/L Dichotomine B have no effect on normal BV2 cells. Further mechanism investigation showed that TAK-242 and Dichotomine B significantly inhibited the protein and mRNA expression levels of TLR4, MyD88, p-mTOR/mTOR (mTOR), p62, p-RPS6/RPS6 (RPS6) and increased the protein and mRNA expression levels of LC3Ⅱ/LC3Ⅰ (LC3B), Beclin-1. Docking study showed the LibDock scores of Dichotomine B with TLR4, MyD88 and mTOR were all higher than those of positive drugs (Diazepam). These findings indicated that Dichotomine B attenuated neuroinflammatory responses in LPS/ATP-induced BV2 microglia, and its mechanism may be related to TLR4/MyD88-mTOR signaling pathway and autophagy.
Versatile aliphatic polyester biosynthesis system for producing random and block copolymers composed of 2-, 3-, 4-, 5-, and 6-hydroxyalkanoates using the sequence-regulating polyhydroxyalkanoate synthase PhaCAR
Authors: Matsumoto Ken'ichiro , Satoh Keigo , Tomita Hiroya , Kawakami Tomoya , Isobe Nagi , Pasquier Loïc , Zinn Manfred 
Published: March 2022

Abstract
BackgroundPolyhydroxyalkanoates (PHAs) are microbial polyesters synthesized by PHA synthase. Naturally occurring PHA copolymers possess a random monomer sequence. The development of PhaCAR, a unique sequence-regulating PHA synthase, has enabled the spontaneous biosynthesis of PHA block copolymers. PhaCAR synthesizes both a block copolymer poly(2-hydroxybutyrate)-b-poly(3-hydroxybutyrate) [P(2HB)-b-P(3HB)], and a random copolymer, poly(3HB-co-3-hydroxyhexanoate), indicating that the combination of monomers determines the monomer sequence. Therefore, in this study, we explored the substrate scope of PhaCAR and the monomer sequences of the resulting copolymers to identify the determinants of the monomer sequence. PhaCAR is a class I PHA synthase that is thought to incorporate long-main-chain hydroxyalkanoates (LMC HAs, >C3 in the main [backbone] chain). Thus, the LMC monomers, 4-hydroxy-2-methylbutyrate (4H2MB), 5-hydroxyvalerate (5HV), and 6-hydroxyhexanoate (6HHx), as well as 2HB, 3HB, and 3-hydroxypropionate (3HP) were tested.ResultsRecombinant Escherichia coli harboring PhaCAR, CoA transferase and CoA ligase genes was used for PHA production. The medium contained the monomer precursors, 2HB, 3HB, 3HP, 4H2MB, 5HV, and 6HHx, either individually or in combination. As the result, homopolymers were obtained only for 3HB and 3HP. Moreover, 3HB and 3HP were randomly copolymerized by PhaCAR. 3HB-based binary copolymers P(3HB-co-LMC HA)s containing up to 2.9 mol% 4H2MB, 4.8 mol% 5HV, or 1.8 mol% 6HHx were produced. Differential scanning calorimetry analysis of the copolymers indicated that P(3HB-co-LMC HA)s had a random sequence. In contrast, combining 3HP and 2HB induced the synthesis of P(3HP)-b-P(2HB). Similarly, P(2HB) segment-containing block copolymers P(3HB-co-LMC HA)-b-P(2HB)s were synthesized. Binary copolymers of LMC HAs and 2HB were not obtained, indicating that the 3HB or 3HP unit is essential to the polymer synthesis. ConclusionPhaCAR possesses a wide substrate scope towards 2-, 3-, 4-, 5-, and 6-hydroxyalkanoates. 3HB or 3HP units are essential for polymer synthesis using PhaCAR. The presence of a 2HB monomer is key to synthesizing block copolymers, such as P(3HP)-b-P(2HB) and P(3HB-co-LMC HA)-b-P(2HB)s. The copolymers that did not contain 2HB units had a random sequence. This study’s results provide insights into the mechanism of sequence regulation by PhaCAR and pave the way for designing PHA block copolymers.
The role of autophagy mediated by HIF-1α/BNIP3 signaling pathway in missed abortion
Authors: Kou Junna , Yan Guangwei , Zeng Xiannxu , Zhang Yurong , Ding Yanzi , Ma Xiaotian , Yuan Enwu 
Published: March 2022

Abstract
Purpose: To investigate the expression of autophagy mediated by HIF-1α/BNIP3 signaling pathway in villous tissues of missed abortion and HTR-8/SVneo cells ,and to elucidate the role of autophagy in missed abortion.Methods: Villous tissues from 30 healthy women with normal pregnancy and 35 patients with missed abortion were collected, HTR-8/SVneo cells were cultured under hypoxia and transfected with HIF-1α-siRNA.Real-time PCR was utilized to measure the expression levels of HIF-1αmRNA and BNIP3mRNA; Western blot was performed to determine the expression levels of HIF-1α、BNIP3、LC3 Ⅱ/Ⅰand Beclin 1 in villous tissues and HTR-8/SVneo cells. Cellular invasion activity was detected by transwell metrigel assay.The level of autophagy were confirmed by the transmission electron microscopy of autophagosome/autophagolysosome formation.Results: The BNIP3 mRNA levels was significantly higher in the missed abortion villous than in control samples,but HIF-1α mRNA levels was similar between the two groups.The protein levels of HIF-1α、BNIP3、Beclin 1 and LC3Ⅱ/Ⅰwere significantly decreased in villous tissues from missed abortion;as well as the autophagic bodies were significantly decreased in villous tissues from missed abortion group. Under hypoxia,HIF-1α and BNIP3mRNA expression was inhibited after silencing HIF-1α by RNAi，while protein expressions of HIF-1α,BNIP3,Beclin1 and LC3Ⅱ/LC3Ⅰwere significantly down-regulated.The number of invading cells was significantly decreased after silencing HIF-1α by RNAi,and the autophagic bodies were significantly decreased after silencing HIF-1α by RNAi in HTR-8/SVneo.Conclusion:Autophagy mediated by HIF-1α/BNIP3 signaling pathway in the villous trophoblast cells may be associated with progression and development of missed abortion.
Effects of neuraxial analgesia technique on labor and maternal-fetal outcomes: a retrospective study
Authors: Lazzari Cecilia , Raffaelli Ricciarda , D’Alessandro Roberto , Simonetto Chiara , Bosco Mariachiara , Zorzato Pier Carlo , Uccella Stefano , Taddei Fabrizio , Franchi Massimo , Garzon Simone 
Published: March 2022

Abstract
Purpose: To compare the effects of epidural analgesia (EA) and combined spine epidural analgesia (SEA) on labor and maternal-fetal outcomes.Methods: We retrospectively identified and included 1499 patients with a single cephalic fetus who delivered at the study center from January 2015 to December 2018 and received neuraxial analgesia at the beginning of the active phase of labor (presence of regular painful contractions and cervical dilatation between 4 and 6 cm). Data including analgesia, labor characteristics, and maternal-fetal outcomes were retrieved from the prospectively collected delivery room database and medical records.Results: SEA was associated with a shorter first stage of labor than EA, with a median difference of 60 minutes. On multivariable ordinal logistic regression analysis, neuraxial analgesia, gestational age, fetal weight, labor induction, and parity were independently associated with the first stage length: patients in the EA group were 1.32 times more likely to have a longer first stage of labor (95% CI 1.06-1.64, p=0.012) than those in the SEA group. Additionally, a significantly lower incidence of fundal pressure was performed among patients who underwent SEA (OR 0.55, 95% CI 0.34-0.9, p=0.017). No associations were observed between the used neuraxial analgesia technique and other outcomes.Conclusions: SEA was associated with a shorter length of the first stage of labor and a lower rate of fundal pressure use than EA. Further studies confirming the effects of SEA on labor management and clarifying differences in maternal-fetal outcomes will allow concluding about the superiority of one technique upon the other.
Multi-task convolutional neural networks for predicting in vitro clearance endpoints from molecular images
Authors: Mora Andrés Martínez , Subramanian Vigneshwari , Miljković Filip 
Published: March 2022

Abstract
Optimization of compound metabolic stability is a highly topical issue in pharmaceutical research. Accordingly, application of predictive in silico models can potentially reduce the number of design-make-test-analyze iterations and consequently speed up the progression of novel candidate molecules. Herein, we have investigated the question if multiple in vitro clearance endpoints could be accurately predicted from image-based molecular representations. Thus, compound measurements for four commonly investigated clearance endpoints were curated from AstraZeneca internal sources, providing a sound basis for building multi-task convolutional neural network models. Application of several increasingly challenging data splitting strategies confirmed that convolutional neural network models were successful at capturing implicit chemical relationships contained in training and test data, similar to what is commonly observed for structural fingerprints. Furthermore, model benchmarking against state-of-the-art machine learning methods, including deep neural networks, trained with standard structure-based representations revealed on par or increased accuracy of convolutional neural networks with clear benefit of multi-task learning across all clearance endpoints. Our findings indicate that image-based molecular representations can be applied to predict multiple clearance endpoints, suggesting a potential follow-up to investigate model interpretability from molecular images.
Integrated bioinformatics analysis of miR-497/195 cluster network in cervical carcinoma
Authors: Karunakara Shreyas Hulusemane , Eswaran Sangavi , Mallya Sandeep , Suresh Padmanaban S , Chakrabarty Sanjiban , Kabekkodu Shama Prasada 
Published: March 2022

Abstract
The miR-497/195 located at 17p13.1 is a highly conserved miRNA cluster whose abnormal expression is emerging as a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 to determine the prognostic utility and its role in cervical cancer (CC) using publicly available datasets. The in-silico analysis and validation identified the cluster as downregulated in CC. A total of 60 target genes were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for in silico functional enrichment, PPIN networks, hub gene identification, immune infiltration correlation, histopathological expressions, and metastatic potential of miR-497/195-5p and their target genes. The PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as top 10 hub genes (HGs). Further, miR-497-5p, RCAN3, RECK, OSBPL3, ATD5, BCL2, and HIST1H3H were shown to affect the overall survival in CC. We have identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 with metastatic potential. Besides 8 druggable genes targeted by 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.
Desulfofustis limnaeus sp. nov., a freshwater sulfate-reducing bacterium isolated from marsh and emended description of the genus Desulfofustis
Authors: Watanabe Miho , Takahashi Ayaka , Kojima Hisaya , Miyata Naoyuki , Fukui Manabu 
Published: March 2022

Abstract
A novel sulfate-reducing bacterium, strain PPLLT, was isolated from marsh soil. Cells of strain PPLLT were rod-shaped with length of 1.5 µm and width of 0.7 µm. Growth was observed at 22–37°C (optimum 35°C) and pH 6.8–8.4 (optimum 7.3). Lactate, succinate, fumarate and malate were utilized as electron donors. Fermentative growth was not occurred on tested organic acids. Besides sulfate, sulfite, thiosulfate and elemental sulfur were utilized as electron acceptors. Major fatty acid was C16:0. The complete genome of strain PPLLT was composed of a circular chromosome with length of 4.2 Mbp and G + C content of 57.7 mol%. Sequence analysis of the 16S rRNA gene showed that strain PPLLT was affiliated with the genus Desulfofustis in the family ‘Desulfocapsaceae’. On the basis of differences in the phylogenetic and phenotypic properties between the strain and the type strain of the genus Desulfofustis, strain PPLLT (= DSM 110475T = JCM 39161T) is proposed as the type strain of a new species, with name of Desulfofustis limnaeus sp. nov.
Cholesterol Analogs Ginsenosides Rg1 and Compound K Control Temozolomide Resistance in Glioblastoma Cells by Regulating Cholesterol Efflux and Lipid Raft Distribution
Authors: Qiu Runze , Zhang Jingjing , Ge Chun , Zhong Yue , Li Qingquan , Li Yingbin , Fan Hongwei 
Published: March 2022

Abstract
Enriched cholesterol in brain is involved in the resistance of glioblastoma to temozolomide treatment. Cholesterol efflux and lipid raft redistribution contribute to improving resistance. Ginsenosides are structurally similar to cholesterol and can alter cholesterol metabolism and lipid raft distribution, whose subtypes Rb1, Rg1, Rg3 and Compound K showed brain permeability. From CGGA database, the expression of cholesterol efflux gene NR1H3 (LXRα) in tumor tissues of patients treated with temozolomide was positively correlated with long-term survival, and was negatively correlated with multidrug resistance protein (MDR)-1 located in lipid rafts. MDR1 level was correlated with cholesterol uptake (LDLR) and synthesis (SREBF2) genes, suggesting that cholesterol is involved in temozolomide resistance. We demonstrated that cholesterol protected the survival of resistant U251 cells from temozolomide stress, and upregulated MDR1. Resistant U251 cells tended to store cholesterol intracellularly, with weaker cholesterol efflux and LXRα expression to maintain a uniform distribution of lipid rafts. Ginsenosides Rb1, Rg1, Rg3 and Compound K reduced intracellular cholesterol content and promoted cholesterol efflux in resistant cells, making lipid raft distribution no longer uniform. Rg1 and Compound K also upregulated LXRα expression and induced the cytotoxicity of temozolomide in the presence of cholesterol. We further found that cholesterol efflux induction, lipid raft redistribution, and temozolomide sensitization by Rg1 and Compound K were induced through stimulation of LXRα. Therefore, ginsenoside Rg1 and Compound K can control temozolomide resistance in glioblastoma cells by regulating cholesterol metabolism, which are potential synergists for temozolomide therapy.
Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Neonates with Respiratory Distress Syndrome: A Retrospective Cohort Study
Authors: Shi Shanshan , Guo Jie , Liao Lihua , Tu Jiabin , Xiong Jialing , Liao Quanwang , Chen Weihua , Chen Kaihong , Fu Minqiang , Liao Ying 
Published: March 2022

Abstract
Background: Respiratory distress syndrome (RDS) is one of the leading causes of neonatal death in the neonatal intensive care unit (NICU). Previous studies have suggested that the development of neonatal RDS may be associated with inflammation and lead to organ dysfunction. The neonatal sequential organ failure assessment (nSOFA) scoring system is an operational definition of organ dysfunction, but whether it can be used to predict mortality in neonates RDS is unknown. The aim of this study was to clarify the performance of the nSOFA score in predicting mortality in patients with neonatal RDS.Method: Neonates with RDS were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. A cox proportional hazards model were used to assess the association between nSOFA score and mortality. Multiple imputation and propensity score matched analysis were used to assess the robustness of the analytical results.Results: In this study of 1281 patients with RDS of which 57.2% were male, death occurred in 40 cases (3.1%). Patients with high nSOFA scores had a higher mortality rate of 10.7% compared with low nSOFA scores at 0.3%. After adjusting for confounding, multivariate cox proportional risk analysis showed that an increase in nSOFA score was significantly associated with increased mortality in patients with RDS [adjusted Hazards Ratio (aHR): 1.46, 95% Confidence Interval (CI): 1.30-1.64; P < 0.001]. Similarly, the High nSOFA group was significantly associated with higher mortality in RDS patients (aHR: 17.40, 95% CI: 3.93-77.02; P < 0.001) compared with the low nSOFA group.Conclusion: The nSOFA score was positively associated with the risk of mortality in cases of neonatal RDS in the NICU, where its use may help clinicians to quickly and accurately identify high risk neonates and implement more aggressive intervention.
A novel automatic quantification protocol for biomarkers of tauopathies in the hippocampus and entorhinal cortex of post-mortem samples using an extended semi-Siamese U-Net
Authors: Gutierrez-Rodriguez Andres E. , Campero-García Luis A. , Martinez-Maldonado Alejandra , Luna-Muñoz José , Cantoral-Ceballos Jose A. , Ontiveros-Torres Miguel A. 
Published: March 2022

Abstract
Through various imaging techniques, efforts have been made to diagnose and predict the course of different neurodegenerative diseases, which significantly increase their morbidity and mortality in the human population over the years, especially proteinopathies where the Tau polypeptide is a key participant in molecular pathogenesis. However, this standard approach to explore the phenomenon of neurodegener-ation has not been directed at understanding the molecular mechanism that causes the aberrant polymeric and fibrillar behavior of Tau protein in the neurofibrillary tangles that replace neuronal populations comprising the hippocampal formation and cortical regions of clinical cases with various proteinopathies. Our main objective was to implement a novel approach based on computational seg-mentation protocols in triple-labeled immunofluorescence imaging with different biomarkers based on pathological post-translational modifications undergone by Tau in brains of patients with tauopathies, implementing an adaptation of the U-Net neural network architecture. Importantly, we used the resulting segmentation masks and significantly quantified the individual and combined fluorescent signals of the different molecular changes Tau underwent in neurofibrillary tangles as individual study structures. Then, we separated them from the rest of the quadrant, detecting unconventional interaction signals between the different biomarkers. Our algorithm provides information that will be fundamental to understand the pathogenesis of dementias with another computational analysis approach in subsequent studies.
Prediction of cardiovascular disease risk in patients with psoriasis in northern China
Authors: Fu Qian , Su Dong qiang , Miao Yu , Chen Taoyu , Ji Yanqi , Zhang Feng 
Published: March 2022

Abstract
To investigate cardio vascular disease (CVD) risk factors and predict future CVD risk in patients with psoriasis in northern China, we conducted a retrospective study on risk factors in 1,067 psoriasis patients (psoriasis group) and 1,110 physical examiners without psoriasis (control group). Compared with the control group, the psoriasis group showed a stronger correlation with CVD history, body mass index, hypertension, diabetes mellitus, and dyslipidaemia (all P < 0.01). CVD was more common in patients with a long history of psoriasis (P < 0.01), and the incidence of severe psoriasis with diabetes was higher (P < 0.01). In the psoriasis prediction group, the proportion in psoriasis in the "medium risk" and "very high risk" was significantly higher (P < 0.01). Heart age was significantly increased than their actual in the "old people" (P < 0.01). The results showed that the risk factors for CVD in patients with psoriasis were higher than those in the control group, and psoriasis with a long history or severe disease had a higher risk of CVD. Patients with psoriasis have a higher risk of future CVD, and the predicted heart age in the older groups tends to exceed the actual age. This suggests that attention should be paid to the present and future risk of CVD in patients with psoriasis and to the management of cardiovascular comorbidities.