bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploiting epigenetics for the treatment of inborn errors of metabolism
Authors: Rutten Martijn G. S. , Rots Marianne G. , Oosterveer Maaike H. 
Published: March 2019

AbstractGene therapy is currently considered as the optimal treatment for inborn errors of metabolism (IEMs), as it aims to permanently compensate for the primary genetic defect. However, emerging gene editing approaches such as CRISPR‐Cas9, in which the DNA of the host organism is edited at a precise location, may have outperforming therapeutic potential. Gene editing strategies aim to correct the actual genetic mutation, while circumventing issues associated with conventional compensation gene therapy. Such strategies can also be repurposed to normalize gene expression changes that occur secondary to the genetic defect. Moreover, besides the genetic causes of IEMs, it is increasingly recognized that their clinical phenotypes are associated with epigenetic changes. Because epigenetic alterations are principally reversible, this may offer new opportunities for treatment of IEM patients. Here, we present an overview of the promises of epigenetics in eventually treating IEMs. We discuss the concepts of gene and epigenetic editing, and the advantages and disadvantages of current and upcoming gene‐based therapies for treatment of IEMs.
Toward a better definition of EPCAM deletions in Lynch Syndrome: Report of new variants in Italy and the associated molecular phenotype
Authors: Cini Giulia , Quaia Michele , Canzonieri Vincenzo , Fornasarig Mara , Maestro Roberta , Morabito Alberto , D'Elia Angela Valentina , Urso Emanuele Damiano , Mammi Isabella , Viel Alessandra 
Published: March 2019

AbstractBackgroundInherited epimutations of Mismatch Repair (MMR) genes are responsible for Lynch Syndrome (LS) in a small, but well defined, subset of patients. Methylation of the MSH2 promoter consequent to the deletion of the upstream EPCAM gene is found in about 1%–3% of the LS patients and represents a classical secondary, constitutional and tissue‐specific epimutation. Several different EPCAM deletions have been reported worldwide, for the most part representing private variants caused by an Alu‐mediated recombination.Methods712 patients with suspected LS were tested for MMR mutation in our Institute. EPCAM deletions were detected by multiplex ligation‐dependent probe amplification (MLPA) and then defined by Long‐Range polymerase chain reaction (PCR)/Sanger sequencing. A comprehensive molecular characterization of colorectal cancer (CRC) tissues was carried out by immunohistochemistry of MMR proteins, Microsatellite Instability (MSI) assay, methylation specific MLPA and transcript analyses. In addition, somatic deletions and/or variants were investigated by MLPA and next generation sequencing (NGS).ResultsAn EPCAM deletion was found in five unrelated probands in Italy: variants c.556‐490_*8438del and c.858+1193_*5826del are novel; c.859‐1430_*2033del and c.859‐670_*530del were previously reported. All probands were affected by CRC at young age; tumors showed MSI and abnormal MSH2/MSH6 proteins expression. MSH2 promoter methylation, as well as aberrant in‐frame or out‐of‐frame EPCAM/MSH2 fusion transcripts, were detected in CRCs and normal mucosae.ConclusionAn EPCAM deletion was the causative variant in about 2% of our institutional series of 224 LS patients, consistent with previously estimated frequencies. Early age and multiple CRCs was the main clinical feature of this subset of patients.
The Matrix Metalloproteinase‐13 Inhibitor Poricoic Acid ZI Ameliorates Renal Fibrosis by Mitigating Epithelial‐Mesenchymal Transition
Authors: Chen Lin , Cao Gang , Wang Ming , Feng Ya‐Long , Chen Dan‐Qian , Vaziri Nosratola D. , Zhuang Shougang , Zhao Ying‐Yong 
Published: March 2019

ScopeFibrosis plays a key role in the progression of various diseases. Matrix metalloproteinases (MMPs) are important for epithelial‐mesenchymal transition (EMT), which contributes to organ fibrosis. Four new poricoic acids are identified, poricoic acid ZI, ZJ, ZK, and ZL, as novel MMP inhibitors from edible mushroom Poria cocos.MethodsMolecular docking, siRNA techniques, TGF‐β1‐treated renal cells, and unilateral ureteral obstructed (UUO) mice are used to explore the potential efficacy of the novel MMP inhibitors in mitigating the fibrotic process.ResultsTreatment with four poricoic acids downregulates profibrotic protein expression in TGF‐β1‐induced HK‐2 cells. Similar results are observed in NRK‐52E and NRK‐49F cells, indicating that poricoic acids can suppress EMT. Furthermore, both in vitro and in vivo experiments demonstrate that poricoic acid ZI (PZI) exerts a stronger inhibitory effect on protein expression and enzymatic activity of MMP‐13 than the other three compounds, which is consistent with the docking results. The inhibitory effect of PZI on MMP‐13 is partially attenuated by MMP‐13 RNAi in HK‐2 cells and UUO mice.ConclusionsThe findings indicate that as a specific MMP‐13 inhibitor, PZI attenuates EMT and renal fibrosis. Therefore, the MMP‐13 inhibitor PZI can be a novel therapeutic candidate for limiting EMT and renal fibrosis.
The effect of orthodontic appliances on oral microflora: A case‐control study
Authors: Dallel Ines , Merghni Abderrahmen , Ben Tanfouss Safa , Tobji Samir , Ben Amor Adel , Mastouri Maha 
Published: March 2019

AbstractAimSeveral studies have shown that orthodontic treatment affects oral flora. The aim of this study was to evaluate the effect of orthodontic treatment on the oral environment.Materials and MethodsOne hundred and one healthy subjects, divided into two groups, were included in this study. The control group consisted of 51 subjects and the test group included 50 patients wearing orthodontic fixed appliances. The microbiological analyses of saliva and bacterial supra‐gingival plaque were performed for the two groups.ResultsThe results showed that fixed orthodontic appliances alter the oral microbial flora, with a significant predominance of opportunistic Staphylococcus aureus in the oral cavity of patients after orthodontic treatment with fixed appliances.ConclusionOrthodontic appliances may act as a reservoir for opportunistic pathogens. Hence, our findings underline the necessity of paying more attention to the prevalence of opportunistic bacteria after orthodontic treatment.
Delayed onset of smooth muscle cell differentiation leads to hydroureter formation in mice with conditional loss of the zinc finger transcription factor gene Gata2 in the ureteric mesenchyme
Authors: Weiss Anna‐Carina , Bohnenpoll Tobias , Kurz Jennifer , Blank Patrick , Airik Rannar , Lüdtke Timo H , Kleppa Marc‐Jens , Deuper Lena , Kaiser Marina , Mamo Tamrat M , Costa Rui , von Hahn Thomas , Trowe Mark‐Oliver , Kispert Andreas 
Published: March 2019

AbstractThe establishment of the peristaltic machinery of the ureter is precisely controlled to cope with the onset of urine production in the fetal kidney. Retinoic acid (RA) has been identified as a signal that maintains the mesenchymal progenitors of the contractile smooth muscle cells (SMCs), while WNTs, SHH, and BMP4 induce their differentiation. How the activity of the underlying signalling pathways is controlled in time, space, and quantity to activate coordinately the SMC programme is poorly understood. Here, we provide evidence that the Zn‐finger transcription factor GATA2 is involved in this crosstalk. In mice, Gata2 is expressed in the undifferentiated ureteric mesenchyme under control of RA signalling. Conditional deletion of Gata2 by a Tbx18cre driver results in hydroureter formation at birth, associated with a loss of differentiated SMCs. Analysis at earlier stages and in explant cultures revealed that SMC differentiation is not abrogated but delayed and that dilated ureters can partially regain peristaltic activity when relieved of urine pressure. Molecular analysis identified increased RA signalling as one factor contributing to the delay in SMC differentiation, possibly caused by reduced direct transcriptional activation of Cyp26a1, which encodes an RA‐degrading enzyme. Our study identified GATA2 as a feedback inhibitor of RA signalling important for precise onset of ureteric SMC differentiation, and suggests that in a subset of cases of human congenital ureter dilatations, temporary relief of urine pressure may ameliorate the differentiation status of the SMC coat. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Application of UPLC‐MS/MS to simultaneously detect four bioactive compounds in the tumour‐shrinking decoction (FM1523) for uterine fibroids treatment
Authors: Cheng Issac Chi‐Chung , Li Ren‐Kai , Leung George Pak‐Heng , Li Song‐Lin , Kong Ming , Lao Li‐Xing , Zhang Zhang‐Jin , Lin Wai‐Ling , Ng Ernest Hung‐Yu , Rong Jian‐Hui , Chen Jian‐Ping , Su Jing , Zhang Kalin Yan‐Bo , Meng Wei 
Published: March 2019

AbstractIntroductionThe Chinese medicine formulation, tumour‐shrinking decoction (TSD, FM1523), which consists of 15 natural medicines, is used for uterine fibroids (UFs) therapy and possesses excellent clinical therapeutic effect.ObjectiveTo develop a sensitive and validated analytical method for the simultaneous quantification of four crucial bioactive compounds including isorhamnetin‐3‐O‐neohesperidoside, curcumin, peimine and tetrahydropalmatine in the principal formulation of this decoction.MethodsAn ultra‐performance liquid chromatography coupled tandem mass spectrometry (UPLC‐MS/MS) with an electrospray ionisation (ESI) source in multiple reaction monitoring (MRM) mode was conducted to investigate these bioactive compounds in the TSD. The chromatographic separation was performed on a C18 column when the flow rate was adjusted at 0.2 mL/min with gradient elution of acetonitrile–water with 0.1% formic acid. Accelerated solvent extraction (ASE) method with higher extraction efficiency was employed for TSD sample pre‐treatment.ResultsThe linearity, limit of detection (LOD) and limit of quantification (LOQ) were determined for this analytical method. The mean recoveries of the compounds were determined between 100.23% and 104.02% with satisfactory relative standard deviation (RSD) in the ranges of 2.65% to 3.81%. The precision was evaluated by intra‐day and inter‐day tests, which revealed RSD within the ranges of 1.21% to 2.14% and 1.24% to 2.32%, respectively.ConclusionThe bioactive compounds of TSD samples were successfully quantified via UPLC‐MS/MS with MRM mode. This study could help to evaluate the pharmacokinetic study of TSD during clinical applications and present a facile strategy for quantifying bioactive compounds in traditional Chinese Medicine decoction.
Mother‐to‐child transmission of hepatitis B virus after amniocentesis: A retrospective matched cohort study
Authors: Han Zhenyan , Zhang Yuan , Bai Xiaoyi , Yin Yuzhu , Xu Chengfang , Hou Hongying 
Published: March 2019

AbstractObjectiveThe objective of this study is to determine whether amniocentesis increases the risk of mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV) and evaluate risk factors for MTCT.MethodsOne hundred forty‐three hepatitis B surface antigen (HBsAg)–positive women with amniocentesis were enrolled into the amniocentesis group. Six hundred five nonamniocentesis cases were matched with amniocentesis cases based on maternal viral loads, antiviral therapy regimens, and delivery dates. MTCT of HBV was defined as HBsAg and/or DNA positivity in infants from birth to age 7 to 12 months.ResultsMother‐to‐child transmission rate was significantly higher in HBsAg‐positive women with amniocentesis than in those without amniocentesis (2.80% vs 0.50%; relative risk [RR], 5.64; 95% CI, 1.28‐24.93). In the amniocentesis group, maternal HBV DNA more than or equal to 7.0 log10 IU/mL and hepatitis B e‐antigen (HBeAg) positivity were associated with higher MTCT rates than maternal HBV DNA less than 7.0 log10 IU/mL (10.81% vs 0%, p = .004) and HBeAg negativity (8.16% vs 0%, p = .013), and antiviral therapy reduced MTCT rate from 14.3% to 0% (p = .554) when maternal HBV DNA was more than or equal to 7.0 log10 IU/mL.ConclusionsAmniocentesis increases the risk of MTCT in women with hepatitis B, and maternal HBV DNA more than or equal to 7.0 log10 IU/mL and HBeAg positivity are risk factors for MTCT. Antiviral therapy may be effective to prevent MTCT after amniocentesis in highly viremic mothers.
Preparation and properties of phosphorus‐ and silicon‐modified phenolic resin with high ablation resistance
Authors: Bao Qiuru , Li Wenzhi , Liu Yuan , Wang Qi 
Published: March 2019

ABSTRACTIn order to further improve the ablation resistance of common phenolic resins, a modified phenolic resin containing phosphorus and silicon (SPPR) was synthesized and the corresponding properties were evaluated. With phosphorus and silicon involved in the macromolecule, SPPR showed excellent flame retardancy and obviously enhanced value (44.8%) of the limiting oxygen index. The thermal stability and charring performance of SPPR were greatly improved, with maximum decomposition temperature of over 500 °C and carbon yield of 60.1% in nitrogen. Differential scanning calorimetry indicated that the curing temperature shifted from 157 °C for the conventional phenolic resin to 182 °C for SPPR. Moreover, an improvement of impact strength from 4.3 to 16.5 kJ m−2 confirmed that incorporation of flexible SiO chain had a noticeable effect on the mechanical properties of SPPR. Such a modified phenolic resin has promising application prospects serving as an ablation material with high performance. © 2019 Society of Chemical Industry
High‐efficiency photovoltaic modules on a chip for millimeter‐scale energy harvesting
Authors: Moon Eunseong , Lee Inhee , Blaauw David , Phillips Jamie D. 
Published: March 2019

AbstractPhotovoltaic modules at the millimeter scale are demonstrated in this work to power wirelessly interconnected millimeter‐scale sensor systems operating under low‐flux conditions, enabling applications in the Internet of things and biological sensors. Module efficiency is found to be limited by perimeter recombination for individual cells and shunt leakage for the series‐connected module configuration. We utilize GaAs and AlGaAs junction barrier isolation between interconnected cells to dramatically reduce shunt leakage current. A photovoltaic module with eight series‐connected cells and total area of 1.27 mm2 demonstrates a power conversion efficiency of greater than 26% under low‐flux near‐infrared illumination (850 nm at 1 μW/mm2). The output voltage of the module is greater than 5 V, providing a voltage up‐conversion efficiency of more than 90%. We demonstrate direct photovoltaic charging of a 16‐μAh pair of thin‐film lithium‐ion batteries under dim light conditions, enabling the perpetual operation of practical millimeter‐scale wirelessly interconnected systems.
Systemic Absorption and Side Effects of Locally Injected Glucocorticoids
Authors: Stout Alison , Friedly Janna , Standaert Christopher J. 
Published: March 2019

Local glucocorticoid injections are often used to treat joint, soft tissue, or spinal pain, but the systemic side effects associated with these injections are poorly understood and not well recognized. There are significant known risks to systemic administration of glucocorticoids. However, there are no guidelines that address issues of systemic absorption, overall systemic risks, or other side effects of locally injected glucocorticoids. For this review, a literature search was performed, and the available evidence on systemic absorption and clinical side effects of intra‐articular and epidural glucocorticoids was synthesized. The goal was to improve clinical understanding of risks associated with these injections. Existing data suggest there is significant individual variability in the amount of systemic absorption and clinical effects of locally injected glucocorticoids. However, it is clear that both intra‐articular and epidural injections can have systemic effects for weeks and that complications may be associated with their use, including Cushing syndrome, loss of bone density, infection, and hyperglycemia. The concurrent use of oral steroids, the number of injections, and the type and dose of glucocorticoids used all are important considerations in estimating risks. The total dose calculation of cumulative glucocorticoid exposure should include all local injections. Caution should be exercised when local glucocorticoid injections are used in higher risk patients, such as postmenopausal women, people with diabetes, and those considering surgery in the near term. Better provider awareness of possible systemic risks should improve decision making and informed consent with patients when considering intra‐articular and epidural steroid injections for painful conditions.Level of EvidenceIV
Structural origin for the strain rate dependence of mechanical response of fluoroelastomer F2314
Authors: Chang Jiarui , Lin Yuanfei , Chen Wei , Tian Fucheng , Chen Pinzhang , Zhao Jingyun , Li Liangbin 
Published: March 2019

ABSTRACTThe structural evolution of fluoroelastomer F2314 is studied during uniaxial tensile in a large strain rate range (0.1–150 s−1) with the combination of a homemade high‐speed stretching device and in situ small‐ and wide‐angle X‐ray scattering techniques. Based on the mechanical behaviors and structural evolutions, three strain rate regions (I–III) are defined. The microphase‐separated structure plays an important role in the mechanical response of F2314. In Region I, deformation of soft domains is the main process before yielding, accompanied by the destruction of lamellar crystals in hard domains. In the stress plateau zone, deformation of hard domains is confirmed as the primary mechanism of energy dissipation. With the orientation parameter of the amorphous phase reaching a critical value, strain hardening is triggered. Recrystallization also takes place in strain hardening zone. In Region II, due to the mismatch between the mobility of molecular chains in hard domains and the acting time of stress, large deformation of hard domains is more and more difficult to occur with the disappearance of recrystallization. In Region III, as almost all molecular chains have no time to adjust or relax to fit the stress field, the sample presents a brittle fracture. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 607–620
Extracellular Vesicles Released by Allogeneic Human Cardiac Stem/Progenitor Cells as Part of Their Therapeutic Benefit
Authors: Hocine Hocine Rachid , Brunel Simon , Chen Qian , Giustiniani Jerome , San Roman Mabel Jouve , Ferrat Yann J. , Palacios Itziar , Rosa Olga , Lombardo Eleuterio , Bensussan Armand , Charron Dominique , Jabrane-Ferrat Nabila , Al-Daccak Reem 
Published: March 2019

Abstract
The positive effects of therapeutic human allogeneic cardiac stem/progenitor cells (hCPC) in terms of cardiac repair/regeneration are very likely mediated by paracrine effects. Our previous studies revealed the advantageous immune interactions of allogeneic hCPC and proposed them as part of the positive paracrine effects occurring upon their application postmyocardial infarction (MI). Currently, extracellular vesicles/exosomes (EV/Exs) released by stem/progenitor cells are also proposed as major mediators of paracrine effects of therapeutic cells. Along this line, we evaluated contribution of EV/Exs released by therapeutic hCPC to the benefit of their successful allogeneic clinical application. Through tailored allogeneic in vitro human assay models mimicking the clinical setting, we demonstrate that hCPC-released EV/Exs were rapidly and efficiently up-taken by chief cellular actors of cardiac repair/regeneration. This promoted MAPK/Erk1/2 activation, migration, and proliferation of human leukocyte antigens (HLA)-mismatched hCPC, mimicking endogenous progenitor cells and cardiomyocytes, and enhanced endothelial cell migration, growth, and organization into tube-like structures through activation of several signaling pathways. EV/Exs also acted as pro-survival stimuli for HLA-mismatched monocytes tuning their phenotype toward an intermediate anti-inflammatory pro-angiogenic phenotype. Thus, while positively impacting the intrinsic regenerative and angiogenic programs, EV/Exs released by therapeutic allogeneic hCPC can also actively contribute to shaping MI-inflammatory environment, which could strengthen the benefits of hCPC allogeneic interactions. Collectively, our data might forecast the application of allogeneic hCPC followed by their cell-free EV/Exs as a strategy that will not only elicit the cell-contact mediated reparative/regenerative immune response but also have the desired long-lasting effects through the EV/Exs. Stem Cells Translational Medicine 2019;8:911–924
Twisting and localization in supergravity: equivariant cohomology of BPS black holes
Authors: Jeon Imtak , Murthy Sameer 
Published: March 2019

Abstract

We develop the formalism of supersymmetric localization in supergravity using the deformed BRST algebra defined in the presence of a supersymmetric background as recently formulated in [1]. The gravitational functional integral localizes onto the cohomology of a global supercharge Q
eq, obeying Q
eq
2
= H, where H is a global symmetry of the background. Our construction naturally produces a twisted version of supergravity whenever supersymmetry can be realized off-shell. We present the details of the twisted graviton multiplet and ghost fields for the superconformal formulation of four-dimensional

$$ \mathcal{N} $$

N

= 2 supergravity. As an application of our formalism, we systematize the computation of the exact quantum entropy of supersymmetric black holes. In particular, we compute the one-loop determinant of the Q
eq

$$ \mathcal{V} $$

V

deformation operator for the off-shell fluctuations of the Weyl multiplet around the AdS2 × S
2 saddle. This result, which is consistent with the corresponding large-charge on-shell analysis, is needed to complete the first-principles computation of the quantum entropy.
Direction of the Biopsy Needle in Ultrasound-Guided Renal Biopsy Impacts Specimen Adequacy and Risk of Bleeding
Authors: Sawicka Katherine , Hassan Noman , Dumaine Chance , Budd Allison , Wall Chris , Banerjee Tamalina , Lim Hyun J. , Mondal Prosanta , Barton James , Moser Michael A.J. 
Published: March 2019

Introduction Although medical factors such as hypertension and coagulopathy have been identified that are associated with hemorrhage after renal biopsy, little is known about the role of technical factors. The purpose of our study was to examine the effects of biopsy needle direction on renal biopsy specimen adequacy and bleeding complications. Methods Two hundred and forty-two patients who had undergone ultrasound-guided renal biopsies were included. A printout of the ultrasound picture taken at the time of the biopsy was used to measure the biopsy angle (“angle of attack” [AOA]) and to determine if the biopsy needle was aimed at the upper or lower pole and if the medulla was targeted or avoided. Results Of the 3 groups of biopsy angle, an AOA of between 50°–70° yielded the most glomeruli per core ( P = .001) and the fewest inadequate specimens (4% vs 15% for > 70°, and 9% for < 50°, P = .038). Biopsy directed at a pole vs an interpolar region resulted in fewer inadequate specimens (8% vs 23%, P = .005), while biopsies that were medulla-avoiding resulted in fewer inadequate specimens (5% vs 16%, P = .004) and markedly reduced bleeding complications (12% vs 46%, P < .001) compared to biopsies where the medulla was entered. Discussion An AOA of approximately 60°, aiming at the poles, and avoiding the medulla were each associated with fewer inadequate biopsies and bleeding complications. While biopsy of the medulla is necessary for some diagnoses, the increased bleeding risk emphasizes the need for communication between nephrologist, pathologist, and radiologist.