bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta‐analysis
Authors: de la Cour Cecilie Dovey , Sperling Cecilie Dyg , Belmonte Federica , Syrjänen Stina , Verdoodt Freija , Kjaer Susanne Krüger 
Published: June 2020

AbstractThe purpose of this systematic review and meta‐analysis was to estimate the overall and type‐specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16INK4a overexpression in relation to HPV‐status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16INK4a overexpression in relation to HPV‐status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6‐38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16INK4a. This meta‐analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.
Structural Diversity‐Oriented Synthesis of Orthogonally Protected Cyclic Amino Acid Derivatives with Multiple Stereogenic Centers
Authors: Nonn Melinda , Remete Attila M. , Kiss Loránd 
Published: June 2020

AbstractThe synthesis of three‐dimensional cyclopentane amino acid derivatives with multiple stereocenters and with high regiochemical and diastereochemical diversity has been achieved starting from cyclopentadiene‐derived β‐aminocyclopentenecarboxylic acid. The small‐molecular design was based on stereo‐ and regiocontrolled functionalization of the starting cyclopentene β‐amino acid through stereoselective oxirane formation/regioselective oxirane opening and resulted in regio‐ and diastereoisomers of novel orthogonally protected aminocyclopentanecarboxylates.
The genomic profile of parathyroid carcinoma based on whole‐genome sequencing
Authors: Hu Ya , Zhang Xiang , Wang Ou , Bi Yalan , Xing Xiaoping , Cui Ming , Wang Mengyi , Tao Wei , Liao Quan , Zhao Yupei 
Published: June 2020

AbstractParathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Although some mutations such as CDC73 have been found in patients, the molecular mechanism of PC still needs extensive data to clarify. Whole‐genome sequencing (WGS) was performed with frozen samples from 23 PC patients. Peripheral leukocytes were collected from 14 patients and served as controls. Somatic and germline gene alterations, copy number abnormalities and structural variants were detected. Inactivating CDC73 mutations were identified in 39.1% of patients, but only one germline inactivating mutation was found. Other cancer‐related mutations identified in more than one case were MAF (2/23), NEB (6/23), NCOR1 (2/23), TTK (2/23), GRIN3A (4/23), TRIO (2/23), MAP1B (2/23), TJP2 (2/23) and FAM20A (2/23). In the seven wild‐type CDC73 samples, the mutated genes were enriched in pathways involving antigen presentation, allograft rejection or autoimmune disease. More copy number variants were found in patients with cancer recurrence (P = .006) and CDC73 mutations (P = .022) than in those without these characteristics. PIK3CA loss was found in one sample, which also harboured a CDC73 mutation. Gene alterations in the PI3K/AKT/mTOR pathway were found in 78.3% (18/23) of tumours. The most prominent cancer‐predisposing mutations were PDE4DIP (15/23), MAP3K1 (13/23) and CDC42EP1 (10/23). In conclusion, the PI3K/AKT/mTOR pathway may be pivotal in PC. CDC73 mutation correlated with an increased mutational burden and tumour relapse. PC patients with wild‐type CDC73 harboured mutations relevant to antigen presentation and autoimmune diseases. A molecular classification based on the CDC73 mutation may help to manage follow‐up and therapy for PC patients.
A pre‐existing coordinated inflammatory microenvironment is associated with complete response of vulvar high‐grade squamous intraepithelial lesions to different forms of immunotherapy
Authors: Abdulrahman Ziena , de Miranda Noel F. C. C. , Hellebrekers Bart W. J. , de Vos van Steenwijk Peggy J. , van Esch Edith M. G. , van der Burg Sjoerd H. , van Poelgeest Mariette I. E. 
Published: June 2020

AbstractImmunotherapy of vulvar high‐grade squamous intraepithelial lesion (vHSIL) is investigated as an alternative for surgery, because of high comorbidity and risk of recurrence. Limited evidence exists on the role and composition of the immune microenvironment in current immunotherapeutic approaches for vHSIL. The vHSIL of 29 patients biopsied before treatment with imiquimod were analyzed by two multiplex seven‐color immunofluorescence panels to investigate the pre‐existing T‐cell and myeloid cell composition in relation to treatment response. The samples were scanned with the Vectra multispectral imaging system. Cells were automatically phenotyped and counted with inForm advanced image analysis software. Cell counts and composition were compared to that of vHSIL patients before therapeutic vaccination (n = 29) and to healthy vulva (n = 27). Our data show that the immune microenvironment of complete responders (CR) to imiquimod resembled the coordinated infiltration with type 1 CD4+ and CD8+ T cells and CD14+ inflammatory myeloid cells also found in healthy vulva. However, more CD8+ T cells and FoxP3+ regulatory T cells were present in CR. The lesions of partial responders (PR) lacked such a coordinated response and displayed an impaired influx of CD14+ inflammatory myeloid cells. Importantly, complete responses after imiquimod or therapeutic vaccination showed the same dependency on a pre‐existing coordinated type 1 T‐cell and CD14+ myeloid cell infiltration. In conclusion, a good clinical outcome after two different forms of immunotherapy for vHSIL is associated with the presence of a primary inflammatory process resulting in the coordinated influx of several types of immune cells which is then amplified.
Long‐term follow‐up of human papillomavirus type replacement among young pregnant Finnish females before and after a community‐randomised HPV vaccination trial with moderate coverage
Authors: Gray Penelope , Kann Hanna , Pimenoff Ville N. , Adhikari Indira , Eriksson Tiina , Surcel Heljä‐Marja , Vänskä Simopekka , Dillner Joakim , Faust Helena , Lehtinen Matti 
Published: June 2020

AbstractLarge scale human papillomavirus (HPV) vaccination against the most oncogenic high‐risk human papillomavirus (HPV) types 16/18 is rapidly reducing their incidence. However, attempts at assessing if this leads to an increase of nonvaccine targeted HPV types have been hampered by several limitations, such as the inability to differentiate secular trends. We performed a population‐based serological survey of unvaccinated young women over 12 years. The women were under 23‐years‐old, residents from 33 communities which participated in a community‐randomised trial (CRT) with approximately 50% vaccination coverage. Serum samples were retrieved pre‐CRT and post‐CRT implementation. Seropositivity to 17 HPV types was assessed. HPV seroprevalence ratios (PR) comparing the postvaccination to prevaccination era were estimated by trial arm. This was also assessed among the sexual risk‐taking core group, where type replacement may occur more rapidly. In total, 8022 serum samples from the population‐based Finnish Maternity Cohort were retrieved. HPV types 16/18 showed decreased seroprevalence among the unvaccinated in communities only after gender‐neutral vaccination (PR16/18A = 0.8, 95% CI 0.7‐0.9). HPV6/11 and HPV73 were decreased after gender‐neutral vaccination (PR6/11A = 0.8, 95% CI 0.7‐0.9, PR73A = 0.7, 95% CI 0.6‐0.9, respectively) and girls‐only vaccination (PR6/11B = 0.8, 95% CI 0.7‐0.9, PR73B = 0.9, 95% CI 0.8‐1.0). HPV68 alone was increased but only after girls‐only vaccination (PR68B = 1.3, 95% CI 1.0‐1.7, PRcore68B = 2.8, 95% CI 1.2‐6.3). A large‐scale, long‐term follow‐up found no type replacement in the communities with the strongest reduction of vaccine HPV types. Limited evidence for an increase in HPV68 was restricted to girls‐only vaccinated communities and may have been due to secular trends (ClinicalTrials.gov number: NCT00534638).
Post‐discharge outcomes for mothers and the mother–infant relationship following admission to a psychiatric Mother–Baby Unit
Authors: Wright Tanya , Stevens Suzanne , Reed Peter W. , Wouldes Trecia A. 
Published: June 2020

ABSTRACTMother–Baby Unit research has focussed on maternal psychopathology over the course of an admission. Less is known about the baby's well‐being, the shared relationship, or the mother's recovery. In an initial sample of 45 women, we describe discharge and post‐discharge outcomes for maternal psychopathology (using maternal report and the Global Assessment of Function, GAF) and the mother–infant relationship (using the Child and Adult Relational Experimental Index, CARE Index). Three months post‐discharge, one third of women described themselves as “completely recovered,” one third were experiencing significant deterioration and 17% were readmitted to inpatient care. Poorer GAF scores were associated with a clinical diagnosis of comorbid personality disorder, antenatal presence of the index illness, partner illicit substance use, maternal perception of her bond, infant social withdrawal, and child protection concern. Post‐discharge, the mother–infant relationship results were concerning. Only 17% were regarded as adequate. Improvement was observed across this period in 56% but relational deterioration occurred for 35%. Maternal and relational outcomes were weakly correlated at discharge (r² = 0.29, p = 0.07) but this was lost post‐discharge (r² = 0.03, p = 0.89). The shared relationship and infant mental health should both be targets for intervention; both during MBU admission, and post‐discharge.
The risk of low risk: First time motherhood, prematurity and dyadic well‐being
Authors: Porter Lauren , van Heugten Kate , Champion Patricia 
Published: June 2020

ABSTRACTPremature birth has a well‐documented impact on infants, mothers and their dyadic interactions. First time motherhood in the context of low risk premature birth—relatively unexplored in the literature—is a specific experience that sits at the nexus of premature infancy, motherhood and the processes that underpin dyadic connection. This qualitative study analyzed semistructured interviews with first time mothers of low risk premature babies. Findings were generated in response to research questions concerning mothers’ meaning‐making, bonding and identity. Findings demonstrated that maternal meaning‐making emerged from a dyadic framework. When mothers or their infants were considered outside of a dyadic context, surplus suffering inadvertently occurred. Findings have important implications for infant mental health practice in medical settings, for postnatal support in the aftermath of premature birth, and for understanding the meaning of risk.
Epigallocatechin‐3‐gallate activates the AMP‐activated protein kinase signaling pathway to reduce lipid accumulation in canine hepatocytes
Authors: Ding Hongyan , Li Yu , Li Wei , Tao Huanqing , Liu Leihong , Zhang Cai , Kong Tao , Feng Shibin , Li Jinchun , Wang Xichun , Wu Jinjie 
Published: June 2020

AbstractEpigallocatechin‐3‐gallate (EGCG) plays a crucial role in hepatic lipid metabolism. However, the underlying regulatory mechanism of hepatic lipid metabolism by EGCG in canine is unclear. Primary canine hepatocytes were treated with EGCG (0.01, 0.1, or 1 μM) and BML‐275 (an AMP‐activated protein kinase [AMPK] inhibitor) to study the effects of EGCG on the gene and protein expressions associated with AMPK signaling pathway. Data showed that treatment with EGCG had greater activation of AMPK, as well as greater expression levels and transcriptional activity of peroxisome proliferator activated receptor‐α (PPARα) along with upregulated messenger RNA (mRNA) abundance and protein abundance of PPARα‐target genes. EGCG decreased the expression levels and transcriptional activity of sterol regulatory element‐binding protein 1c (SREBP‐1c) along with downregulated mRNA abundance and protein abundance of SREBP‐1c target genes. Of particular interest, exogenous BML‐275 could reduce or eliminate the effects of EGCG on lipid metabolism in canine hepatocytes. Furthermore, the content of triglyceride was significantly decreased in the EGCG‐treated groups. These results suggest that EGCG might be a potential agent in preventing high‐fat diet‐induced lipid accumulation in small animals.
Families in posets minimizing the number of comparable pairs
Authors: Balogh József , Petříčková Šárka , Wagner Adam Zsolt 
Published: June 2020

AbstractGiven a graded poset we say a family is centered if it is obtained by ‘taking sets as close to the middle layer as possible.’ A poset is said to have the centeredness property if for any , among all families of size in , centered families contain the minimum number of comparable pairs. Kleitman showed that the Boolean lattice has the centeredness property. It was conjectured by Noel, Scott, and Sudakov, and by Balogh and Wagner, that the poset also has the centeredness property, provided is sufficiently large compared with . We show that this conjecture is false for all and investigate the range of for which it holds. Further, we improve a result of Noel, Scott, and Sudakov by showing that the poset of subspaces of has the centeredness property. Several open questions are also given.
Synthesis, biological evaluation, and docking study of a series of 1,4‐disubstituted 1,2,3‐triazole derivatives with an indole‐triazole‐peptide conjugate
Authors: Suryapeta Srinivas , Papigani Neeraja , Banothu Venkanna , Dubey Pramod Kumar , Mukkanti Khagga , Pal Sarbani 
Published: June 2020

AbstractA series of new compounds containing an indole‐triazole‐peptide conjugate were designed as potential agents possessing the dual anti‐bacterial and anticancer activities. Accordingly, 20 compounds were prepared via a multi‐step synthesis involving the copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) as a key step in moderate to high yield. All the synthesized compounds were purified by chromatographic techniques and characterized by IR, 1H and 13C NMR and mass spectral data. The synthesized derivatives were screened for their antimicrobial activities against one gram‐positive (Staphylococcus aureus) and three gram‐negative (Escherichia coli, Klebsiella pneumonia, and Proteus vulgaris) bacteria using an agar‐well diffusion method. Most of the compounds showed moderate to reasonable antibacterial activities especially the compound 9e that showed good activities against all the strains. The potential of DNA gyrase inhibitory activity of this compound was assessed by using molecular docking studies in silico carried out using Autodock Vina software. The low ΔGbind value (−9.4 Kcal/mol) of compound 9e suggested its good interactions with the target protein in silico. The cytotoxic activities of some of the compounds synthesized were evaluated via a MTT assay using the human lung cancer cell line A549. Several compounds showed promising activities among which compound 9b, 9k, and 9e showed low IC50 values.
The multiple ways Wnt signaling contributes to acute leukemia pathogenesis
Authors: Soares-Lima Sheila C , Pombo-de-Oliveira Maria S , Carneiro Flávia R G 
Published: June 2020

Abstract
WNT proteins constitute a very conserved family of secreted glycoproteins that act as short-range ligands for signaling with critical roles in hematopoiesis, embryonic development, and tissue homeostasis. These proteins transduce signals via the canonical pathway, which is β-catenin-mediated and better-characterized, or via more diverse noncanonical pathways that are β-catenin independent and comprise the planar cell polarity (PCP) pathway and the WNT/Ca++ pathways. Several proteins regulate Wnt signaling through a variety of sophisticated mechanisms. Disorders within the pathway can contribute to various human diseases, and the dysregulation of Wnt pathways by different molecular mechanisms is implicated in the pathogenesis of many types of cancer, including the hematological malignancies. The types of leukemia differ considerably and can be subdivided into chronic, myeloid or lymphocytic, and acute, myeloid or lymphocytic, leukemia, according to the differentiation stage of the predominant cells, the progenitor lineage, the diagnostic age strata, and the specific molecular drivers behind their development. Here, we review the role of Wnt signaling in normal hematopoiesis and discuss in detail the multiple ways canonical Wnt signaling can be dysregulated in acute leukemia, including alterations in gene expression and protein levels, epigenetic regulation, and mutations. Furthermore, we highlight the different impacts of these alterations, considering the distinct forms of the disease, and the therapeutic potential of targeting Wnt signaling.
Aloe emodin relieves Ang II-induced endothelial junction dysfunction via promoting ubiquitination mediated NLRP3 inflammasome inactivation
Authors: Zhang Yi , Song Ziqing , Huang Shan , Zhu Li , Liu Tianyi , Shu Hongyan , Wang Lei , Huang Yi , Chen Yang 
Published: June 2020

Abstract
Recent studies have revealed that aloe emodin (AE), a natural compound from the root and rhizome of Rheum palmatum L., exhibits significant pharmacologic activities. However, the pharmacologic relevance of the compound, particularly for cardiovascular disease, remains largely unknown. Here, we hypothesized that AE could improve endothelial junction dysfunction through inhibiting the activation of NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome regulated by NLRP3 ubiquitination, and ultimately prevent cardiovascular disease. In vivo, we used confocal microscopy to study the expression of tight junction proteins zonula occludens-1/2 (ZO-1/2) and the formation of NLRP3 inflammasome in coronary arteries of hypertension. And the experimental serum was used to detect the activation of NLRP3 inflammasome by ELISA assay. We found that AE could restore the expression of the endothelial connective proteins ZO-1/2 and decrease the release of high mobility group box1 (HMGB1), and also inhibited the formation and activation of NLRP3 inflammasome. Similarly, in vitro, our findings demonstrated that AE could restore the expression of the tight junction proteins ZO-1/2 and decrease monolayer cell permeability that related to endothelial function after stimulation by angiotensin II (Ang II) in microvascular endothelial cells (MECs). We also demonstrated that AE could inhibit Ang II-induced NLRP3 inflammasome formation and activation, which were regulated by NLRP3 ubiquitination in MECs, as shown by fluorescence confocal microscopy and Western blot. Together with these changes, we revealed a new protection mechanism of AE that inhibited NLRP3 inflammasome activation and decreased the release of HMGB1 by promoting NLRP3 ubiquitination. Our findings implicated that AE exhibited immense potential and specific therapeutic value in hypertension-related cardiovascular disease in the early stage and the development of innovative drugs.
The neuroactive substances and associated muscle system in Rhipidocotyle campanula (Digenea, Bucephalidae) from the intestine of the pike Esox lucius
Authors: Kreshchenko Natalia , Terenina Nadezhda , Nefedova Darya , Mochalova Natalia , Voropaeva Ekaterina , Movsesyan Sergey 
Published: June 2020

AbstractWe report about the muscular system and the serotonergic and FMRFamidergic components of the nervous system of the Bucephalidae trematode, Rhipidocotyle campanula, an intestinal parasite of the pike. We use immunocytochemical methods and confocal scanning laser microscopy (CLSM). The musculature is identified by histochemical staining with fluorescently labeled phalloidin. The body wall musculature of R. campanula contains three layers of muscle fibres – the outer thin circular, intermediate longitudinal and inner diagonal muscle fibres running in two opposite directions. The digestive system of R. campanula possess of a well‐developed musculature: radial, longitudinal and circular muscle elements are detected in the pharynx, circular and longitudinal muscle filaments seen in the oesophagus, and longitudinal and the circular muscle fibres were found in the intestinal wall. Specific staining indicating the presence of actin muscle filaments occurs in the cirrus sac localized in the posterior body region. The frontal region of anterior attachment organ, the rhynchus, in R. campanula is represented by radial muscle fibres. The posterior part of the rhynchus comprise of radial muscles forming the organ's wall, and several strong longitudinal muscle bundles. Serotonergic and FMRFamidergic structures are detected in the central and peripheral compartments of the nervous system of R. campanula, that is, in the paired brain ganglia, the brain commissure, the longitudinal nerve cords, and connective nerve commissures. The innervations of the rhynchus, pharynx, oesophagus and distal regions of the reproductive system by the serotonergic and FMRFamidergic nervous elements are revealed. We compare our findings obtained on R. campanula with related data for other trematodes.
Intrinsic disorder in protein sense‐antisense recognition
Authors: Dayhoff Guy W. , van Regenmortel Marc H. V. , Uversky Vladimir N. 
Published: June 2020

AbstractIn addition to the well‐established sense‐antisense complementarity abundantly present in the nucleic acid world and serving as a basic principle of the specific double‐helical structure of DNA, production of mRNA, and genetic code‐based biosynthesis of proteins, sense‐antisense complementarity is also present in proteins, where sense and antisense peptides were shown to interact with each other with increased probability. In nucleic acids, sense‐antisense complementarity is achieved via the Watson‐Crick complementarity of the base pairs or nucleotide pairing. In proteins, the complementarity between sense and antisense peptides depends on a specific hydropathic pattern, where codons for hydrophilic and hydrophobic amino acids in a sense peptide are complemented by the codons for hydrophobic and hydrophilic amino acids in its antisense counterpart. We are showing here that in addition to this pattern of the complementary hydrophobicity, sense and antisense peptides are characterized by the complementary order‐disorder patterns and show complementarity in sequence distribution of their disorder‐based interaction sites. We also discuss how this order‐disorder complementarity can be related to protein evolution.