bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical investigation of oral cancer in adolescent and young adult generation
Authors: Yoshioka Yukio , Sakaue Taishi , Matsui Kensaku , Tsushima Koji , Obayashi Fumitaka , Hamada Atsuko , Yamasaki Sachiko , Hamana Tomoaki , Sumi Kensaku , Kanda Taku , Koizumi Koichi , Tani Ryouji , Hayashido Yasutaka , Sasahara Hisako , Ito Yoku , Sado Tomohiro , Ishida Yasutaka , Okamoto Kosei , Kobayashi Masashi , Sakamoto Akihiko , Myoken Yoshinari , Toratani Shigeaki , Okamoto Tetsuji 
Published: November 2020

AbstractPurposeTo determine the clinical and therapeutic characteristics in adolescent and young adult (AYA) generation with oral cancer.MethodsWe retrospectively studied AYA patients with oral cancer, aged 16‐40 years who visited our department between 1 April 1997 and 31 December 2017, focusing on clinical characteristics including sex, age distribution, tumor site, pathological classification, stage, treatment, treatment outcome, and social rehabilitation.ResultsForty‐two patients of AYA generation (19 males and 23 females), accounting for five. Seven percent of all oral cancer patients (740), were included. Most were aged 35‐39 (median, 30.9) years. The most frequent site of tumor occurrence was the tongue (n = 29) and the most common histological type was squamous cell carcinoma (n = 30). Most patients had T2N0 cancer based on the TNM classification, and early stage II. Thirty‐nine patients underwent radical treatment, comprising 14 cases of surgery, six of chemo‐radiation therapy, four of surgery with chemotherapy, and two of surgery with radiation therapy. Conversely, nine patients underwent radical radiation therapy, comprising five cases of internal radiation therapy and four of chemo‐radiation therapy. The 5‐year overall survival rate in AYA patients with oral cancer (79.67%) was statistically superior to that in the older‐age group (68.48%) (P = .034). Seven deaths were reported because of distant metastasis in cancer types with relatively poor prognosis.ConclusionIn this clinical investigation, treatment outcomes of AYA patients were mostly favorable. Most AYA patients with oral cancer recovered fully after radical treatment and achieved social reintegration.
Does additional monitoring status increase the reporting of adverse drug reactions? An interrupted time series analysis of EudraVigilance data
Authors: Segec Andrej , Slattery Jim , Morales Daniel R. , Januskiene Justina , Kurz Xavier , Arlett Peter 
Published: November 2020

AbstractPurposeTo evaluate the impact of including a medicine in the list of medicinal products subject to additional monitoring (AM) on the reporting of adverse drug reactions (ADRs) in the european economic area (EEA).MethodsInterrupted time series using the monthly number of EEA ADR reports in EudraVigilance during 12 months before and after the addition to AM list. The main outcome was the change (%) in reporting of ADRs with step change as the a priori impact model. Further time series analysis was performed using Joinpoint Regression.ResultsThe analysis included 11 active substances. No significant immediate (step change) increase of reporting was identified for any product at time of addition to AM list. We identified a significant gradual increase of ADR reporting after addition to AM list (slope change) for two out of five new products—boceprevir (10% per month, 95% confidence interval (CI) 3%–18%) and denosumab‐Xgeva (13% per month, 95% CI 4%–22%). No change was identified for Prolia, another denosumab‐containing product not subject to AM. No significant increase was identified for any product included in the AM list due to the requirement to conduct a PASS. Conversely, a gradual decrease in reporting was identified for natalizumab (−5% per month; 95% CI −10% to −1%), rivaroxaban (−5%; −8 to −3%), and varenicline (−16%; −21 to −10%). The results were corroborated by the Joinpoint analyses, which yielded similar results.ConclusionsWe identified limited evidence that reporting of ADRs increased modestly and gradually for some new products and not for products with PASS requirement.
Influence of substituent and push‐pull effect on the chemical shifts of the carbon in bridging bond of 1‐furyl/thienyl‐2‐arylethylene
Authors: Cao Chao‐tun , Yan Lu , Cao Chenzhong , Qu Junyan 
Published: November 2020

AbstractSixty‐six samples of 1‐furyl/thienyl‐2‐arylethylene model compounds XCHCHArY (abbreviated XEBY) were synthesized. The nuclear magnetic resonance spectra (NMR) of model compounds were determined. The chemical shift δC(X) and δC(Y) of the carbon atoms in bridging bond CHCH which connected to the X group and the ArY group, respectively, were confirmed with the two‐dimensional NMR method. The effect of substituent on the δC(X) and δC(Y) was studied, meanwhile, the push‐pull effect of substituent on ΔδC = δC(Y) − δC(X) and δC(Y/X) = δC(Y)/δC(X) were discussed. The results show the following: (a) Both the δC(X) and δC(Y) are affected by excited‐state substituent constant
of group X, Hammett constant σ(Y), and excited‐state substituent constant
of group Y. The effect of σ(Y) on the δC(X) is positive, whereas that on the δC(Y) is negative. That is to say, the σ(Y) of group Y has an alternative influence on the δC(X) and δC(Y). (b) Compared with furyl, there is a p‐d effect formed by the 3d orbit of S atom and the p electron of the π system in thienyl, which increase the chemical shift of the carbon atoms in bridging bond. (c) The push‐pull effect between substituent X and Y is not only affected by the σ parameter but also related to the
parameter, which results from the combined effect of the two parameters σ and
. The observation of this paper provides a new perspective in understanding the push‐pull effect of substituent.
Design of controllers with distributed central pattern generator architecture for adaptive oscillations
Authors: Wu Andy , Iwasaki Tetsuya 
Published: November 2020

SummaryThis article introduces a systematic method for designing a distributed nonlinear controller to achieve multiple distinct gaits, each of which is characterized by a prescribed oscillation profile and velocity, for a class of locomotion systems. We base the controller on the central pattern generator (CPG), a neural circuit which governs repetitive motions, such as walking and swimming, in most animals. First, we establish a general method for designing a nonlinear CPG‐inspired controller to assign a single gait for a linear plant; we show that this problem reduces to an eigenstructure assignment problem for which a solution has recently become available. We then extend the design to an adaptive, structured controller that can adjust the gait in response to variations in the environment. The essential problem becomes a controller design to satisfy different eigenstructure conditions for different plants; a computationally tractable formulation is provided for this problem. We provide two numerical examples using a link‐chain model as a plant representative of animals that move through undulatory motions, such as leeches or eels, to demonstrate the efficacy of this theory. In the first example, we employ an analytical condition for eigenstructure assignment to design an unstructured controller that assigns a single gait for the link‐chain model. The second example searches for a structured controller to assign two different gaits that can be switched using a higher level command.
Chromatin accessibility in canine stromal cells and its implications for canine somatic cell reprogramming
Authors: Questa Maria , Moshref Maryam , Jimenez Robert J. , Lopez-Cervantes Veronica , Crawford Charles K. , Settles Matthew L. , Ross Pablo J. , Kol Amir 
Published: November 2020

Abstract
Naturally occurring disease in pet dogs is an untapped and unique resource for stem cell-based regenerative medicine translational research, given the many similarities and complexity such disease shares with their human counterparts. Canine-specific regulators of somatic cell reprogramming and pluripotency maintenance are poorly understood. While retroviral delivery of the four Yamanaka factors successfully reprogrammed canine embryonic fibroblasts, adult stromal cells remained resistant to reprogramming in spite of effective viral transduction and transgene expression. We hypothesized that adult stromal cells fail to reprogram due to an epigenetic barrier. Here, we performed assay for transposase-accessible chromatin using sequencing (ATAC-seq) on canine stromal and pluripotent stem cells, analyzing 51 samples in total, and establishing the global landscape of chromatin accessibility before and after reprogramming to induced pluripotent stem cells (iPSC). We also studied adult stromal cells that do not yield iPSC colonies to identify potential reprogramming barriers. ATAC-seq analysis identified distinct cell type clustering patterns and chromatin remodeling during embryonic fibroblast reprogramming. Compared with embryonic fibroblasts, adult stromal cells had a chromatin accessibility landscape that reflects phenotypic differentiation and somatic cell-fate stability. We ultimately identified 76 candidate genes and several transcription factor binding motifs that may be impeding somatic cell reprogramming to iPSC, and could be targeted for inhibition or activation, in order to improve the process in canines. These results provide a vast resource for better understanding of pluripotency regulators in dogs and provide an unbiased rationale for novel canine-specific reprogramming approaches.
Microwave‐Assisted Tandem Kornblum Oxidation and Biginelli Reaction for the Synthesis of Dihydropyrimidones
Authors: Malik Asif A. , Dangroo Nisar A. , Ara Tabassum 
Published: November 2020

AbstractA simple and straightforward approach for the synthesis of dihydropyrimidones via sequential Kornblum oxidation/Biginelli reaction has been developed. The protocol involves an in situ oxidation of benzyl halides which serve as a carbonyl equivalents followed by cyclocondensation with (thio) urea and ethylacetoacetate to furnish dihydropyrimidones under catalyst and base free conditions in a one‐pot tandem manner under microwave irradiation. Further, the product purification using aqueous recrystallization avoids large quantities of volatile and a toxic organic solvent usually required for work‐up and very less time required for this process makes the method environmental‐ and nature‐friendly.
Metal Free Sulfonic Acid Functionalized Carbon Catalyst for Green and Mechanochemical Synthesis of Perimidines
Authors: Sahiba Nusrat , Sethiya Ayushi , Soni Jay , Agarwal Shikha 
Published: November 2020

AbstractA new and scalable mechanochemical approach has been developed for the synthesis of perimidine derivatives using an efficient and recyclable catalyst, carbon sulfonic acid under metal‐free conditions. A wide variety of aldehydes displayed cyclo‐condensation reaction with 1,8‐diaminonaphthalene in EtOH under ambient reaction conditionsviagrind‐stone technique to produce substituted perimidines in excellent yields (95–99 %) in a very short reaction time. This method has interesting features like single‐step synthesis, high functional group tolerance, transition‐metal free synthesis, high atom‐economy, recyclable catalyst, no need of tedious purification process, gram‐scale synthesis, high green chemistry matrix (Eco‐score and E‐factor) that make this protocol green and eco‐friendly.
Substituent‐Dependent Absorption Spectra, Electrochemical and Antiproliferative Activity Studies of Some 3‐(4‐(Benzyloxy)phenyl)‐5‐(4‐methoxyphenyl)‐1‐(substitutedphenyl)formazans
Authors: Turkoglu Gulsen , Akkoç Senem 
Published: November 2020

AbstractWe have reported the effect of electron donating and withdrawing substituents on absorption and electrochemical properties of formazan derivatives as well as antiproliferative activity. New formazans F2 and F4 bearing electron donating subunits have been synthesized, and characterized via elemental analysis and various spectroscopic techniques. The substituent effects and solvatochromic of formazan derivatives F2–F5 having different substituents on 1‐phenyl ring in eleven solvents were investigated by absorption spectroscopy. Whilst their absorption bands are only slightly dependent on the polarities of solvents, the considerable alteration was detected by modifying the electronic characteristic and positions of the substituents. Then, the antiproliferative activity of all compounds was investigated in four cancer cell lines using MTT and XTT assay methods. The IC50 values of F2 and F4, having electron donating methoxy and methyl subunits were obtained in the ranges of 10.60 and 21.53 μM in DLD‐1 and HepG2 cell lines. Our study demonstrates that F2 and F4 are more active than the positive control drug used.
Temperature‐Responsive Janus Particles as Microsurfactants for On‐Demand Coalescence of Emulsions
Authors: Hwang Yoon‐Ho , Jeon Kyounghee , Ryu Sang A , Kim Dong‐Pyo , Lee Hyomin 
Published: November 2020

AbstractA new strategy that utilizes temperature‐responsive wax‐based Janus particles as microsurfactants to simultaneously achieve enhanced emulsion stability, as well as, on‐demand coalescence of emulsion droplets is presented. The dumbbell structure with different surface wetting properties on each side of the Janus particle enables the particles to strongly adsorb at the liquid–liquid interface, leading to excellent stability against coalescence for both water‐in‐oil (W/O) and oil‐in‐water (O/W) emulsions. Moreover, these Janus microparticles are composed of a hydrophilic acrylate resin and a hydrophobic wax compartment which transitions from a frozen to an oil‐soluble molten state above the melting point. This allows the particle‐adsorbed droplets to coalesce above a designated temperature, depending on the type of wax material used. It is envisioned that the excellent emulsion stability and the tunable and rapid response to local temperature enabled by the wax‐based Janus particle offers new and exciting opportunities in the advancing technologies including micro‐reactors and drug delivery systems to name a few.
Overlapping mechanisms of lncRNA and expanded microsatellite RNA
Authors: Johnson Sara J. , Cooper Thomas A. 
Published: November 2020

AbstractRNA has major regulatory roles in a wide range of biological processes and a surge of RNA research has led to the classification of numerous functional RNA species. One example is long noncoding RNAs (lncRNAs) that are structurally complex transcripts >200 nucleotides (nt) in length and lacking a canonical open reading frame (ORF). Despite a general lack of sequence conservation and low expression levels, many lncRNAs have been shown to have functionality in diverse biological processes as well as in mechanisms of disease. In parallel with the growing understanding of lncRNA functions, there is a growing subset of microsatellite expansion disorders in which the primary mechanism of pathogenesis is an RNA gain of function arising from RNA transcripts from the mutant allele. Microsatellite expansion disorders are caused by an expansion of short (3–10 nt) repeats located within coding genes. Expanded repeat‐containing RNA mediates toxicity through multiple mechanisms, the details of which remain only partially understood. The purpose of this review is to highlight the links between functional mechanisms of lncRNAs and the potential pathogenic mechanisms of expanded microsatellite RNA. These shared mechanisms include protein sequestration, peptide translation, micro‐RNA (miRNA) processing, and miRNA sequestration. Recognizing the parallels between the normal functions of lncRNAs and the negative impact of expanded microsatellite RNA on biological processes can provide reciprocal understanding to the roles of both RNA species.This article is categorized under:
RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications
RNA in Disease and Development > RNA in Disease
Single particle operators and their correlators in free $$ \mathcal{N} $$ = 4 SYM
Authors: Aprile F. , Drummond J. M. , Heslop P. , Paul H. , Sanfilippo F. , Santagata M. , Stewart A. 
Published: November 2020

Abstract
We consider a set of half-BPS operators in $$ \mathcal{N} $$
N
= 4 super Yang-Mills theory which are appropriate for describing single-particle states of superstring theory on AdS5× S5. These single-particle operators are defined to have vanishing two-point functions with all multi-trace operators and therefore correspond to admixtures of single- and multi-traces. We find explicit formulae for all single-particle operators and for their two-point function normalisation. We show that single-particle U(N) operators belong to the SU(N) subspace, thus for length greater than one they are simply the SU(N) single-particle operators. Then, we point out that at large N, as the length of the operator increases, the single-particle operator naturally interpolates between the single-trace and the S3 giant graviton. At finite N, the multi-particle basis, obtained by taking products of the single-particle operators, gives a new basis for all half-BPS states, and this new basis naturally cuts off when the length of any of the single-particle operators exceeds the number of colours. From the two-point function orthogonality we prove a multipoint orthogonality theorem which implies vanishing of all near-extremal correlators. We then compute all maximally and next-to-maximally extremal free correlators, and we discuss features of the correlators when the extremality is lowered. Finally, we describe a half-BPS projection of the operator product expansion on the multi-particle basis which provides an alternative construction of four- and higher-point functions in the free theory.
Isolation of a gene cluster from Armillaria gallica for the synthesis of armillyl orsellinate–type sesquiterpenoids
Authors: Engels Benedikt , Heinig Uwe , McElroy Christopher , Meusinger Reinhard , Grothe Torsten , Stadler Marc , Jennewein Stefan 
Published: November 2020

AbstractMelleolides and armillyl orsellinates are protoilludene-type aryl esters that are synthesized exclusively by parasitic fungi of the globally distributed genusArmillaria(Agaricomycetes, Physalacriaceae). Several of these compounds show potent antimicrobial and cytotoxic activities, making them promising leads for the development of new antibiotics or drugs for the treatment of cancer. We recently cloned and characterized theArmillaria gallicagenePro1encoding protoilludene synthase, a sesquiterpene cyclase catalyzing the pathway-committing step to all protoilludene-type aryl esters. Fungal enzymes representing secondary metabolic pathways are sometimes encoded by gene clusters, so we hypothesized that the missing steps in the pathway to melleolides and armillyl orsellinates might be identified by cloning the genes surroundingPro1. Here we report the isolation of anA. gallicagene cluster encoding protoilludene synthase and four cytochrome P450 monooxygenases. Heterologous expression and functional analysis resulted in the identification of protoilludene-8α-hydroxylase, which catalyzes the first committed step in the armillyl orsellinate pathway. This confirms that ∆-6-protoilludene is a precursor for the synthesis of both melleolides and armillyl orsellinates, but the two pathways already branch at the level of the first oxygenation step. Our results provide insight into the synthesis of these valuable natural products and pave the way for their production by metabolic engineering.Key points• Protoilludene-type aryl esters are bioactive metabolites produced by Armillaria spp.• The pathway-committing step to these compounds is catalyzed by protoilludene synthase.• We characterized CYP-type enzymes in the cluster and identified novel intermediates.
Nephrocytes are part of the spectrum of filtration epithelial diversity
Authors: Miyaki Takayuki , Kawasaki Yuto , Matsumoto Akira , Kakuta Soichiro , Sakai Tatsuo , Ichimura Koichiro 
Published: November 2020

AbstractThe excretory system produces urine by ultrafiltration via a filtration epithelium. Podocytes are widely found as filtration epithelial cells in eucoelomates. In some animal taxa, including insects and crustaceans, nephrocytes serve to separate toxic substances from the body fluid, in addition to podocytes. Drosophila nephrocytes have been recently utilized as a model system to study podocyte function and disease. However, functionality and cellular architecture are strikingly different between Drosophila nephrocytes and eucoelomate podocytes, and the phylogenetic relationship between these cells remains enigmatic. In this study, using focused-ion beam-scanning electron microscopy (FIB-SEM) tomography, we revealed three-dimensional architecture of decapod nephrocytes with unprecedented accuracy—they filled an enormous gap, which can be called “missing link,” in the evolutionary diversity of podocytes and nephrocytes. Thus, we concluded that nephrocytes are part of the spectrum of filtration epithelial diversity in animal phylogeny.
In vitro blood compatibility evaluation method: incubating while rotating hemodialyzers filled with fresh human blood
Authors: Kamata Kinue , Hatanaka Yoshihiro , Tanaka Hiromi , Inoue Satoru , Tokimizu Yusuke , Tanba Sayuri , Kishikawa Yuki , Koizumi Toshinori 
Published: November 2020

AbstractOne of the often-used methods for in vitro evaluation of the blood compatibility of hemodialysis membranes is the circulation of human blood through a miniaturized hemodialyzer. The use of a rather small amount of human blood in its evaluation is one advantage of this method. However, because it is manufactured by a different process than actual ones, a miniaturized hemodialyzer membrane cannot always preserve the properties of actual hemodialyzers. To address this problem, we established a new experimental method that uses a relatively small amount of human blood and actual dialyzers. In this method, a test hemodialyzer and a control hemodialyzer filled with human blood obtained from the same donor is slowly rotated to prevent spontaneous blood cell sedimentation for 4 h at 37 °C. By use of this method, we were able to compare blood compatibility between a polysulfone (PS) membrane and a vitamin E (VE)-bonded PS membrane in terms of their relative antithrombotic, antioxidative, and anti-inflammatory properties. Consistent with many previous reports, the results clearly showed that compared with the PS membrane, VE-bonded PS membrane is more blood compatible. These findings suggest that our method is applicable, at least to in vitro blood compatibility evaluation of PS type dialysis membranes.
Socio-Sexual Experiences and Access to Healthcare Among Informal PrEP Users in the Netherlands
Authors: van Dijk Mart , de Wit John B. F. , Kamps Rebecca , Guadamuz Thomas E. , Martinez Joel E. , Jonas Kai J. 
Published: November 2020

AbstractThe aim of this qualitative study was to explore the experiences of informal PrEP users regarding access to PrEP and PrEP-related healthcare, community responses, sexual behavior and well-being. We interviewed 30 men who have sex with men (MSM) in semi-structured online interviews between March and August 2018. Interviews were analyzed using interpretive description. Informal PrEP users were well informed about the use of PrEP, but sometimes did not make use of renal testing. Participants reported a lack of PrEP knowledge among healthcare providers, which limited their access to PrEP and put them at risk, as they received incorrect information. Although some participants reported negative reactions from potential sex partners, most received positive reactions and were sometimes seen as more desirable sex partners. PrEP healthcare services should not only be accessible to formal PrEP users, but also to PrEP users who procure PrEP informally.