bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontline Science: Late CD27 stimulation promotes IL-7Rα transcriptional re-expression and memory T cell qualities in effector CD8+ T cells
Authors: Dong Han , Buckner Andrew , Prince Jessica , Bullock Timothy 
Published: June 2019

Abstract
We previously demonstrated that CD27 co-stimulation during a primary CD8+ T-cell response was critical for the expression of IL-7Rα on acute effector CD8+ T cells, providing an essential element in the generation of CD8+ T-cell memory to infectious pathogens. IL-7 plays a critical role in the generation and maintenance of memory CD8+ T cells, and IL-7Rα has been regarded as a functional marker of long-lived memory precursor effector cells. While IL-7Rα is downregulated acutely upon TCR stimulation, the regulation of the emergence of IL-7Rα expressing cells around the peak of primary CD8+ responses is less clear. Re-expression could be a default outcome after withdrawal of TCR stimulation. Alternatively, specific stimuli could actively antagonize the downregulation or promote the recovery of IL-7Rα in Ag-activated CD8+ T cells. By utilizing agonistic mAb and transgenic models, here we show: (1) CD27 stimulation acts directly on CD8+ T cells to enhance IL-7Rα-expressing effectors; (2) CD27 stimulation neither alleviates the downregulation of IL-7Rα upon TCR signaling nor promotes the expansion/survival of IL-7Rα-expressing effectors, but facilitates IL-7Rα re-expression; (3) CD27 stimulation regulates Il7ra mRNA abundance but not protein distribution. Importantly, CD27 stimulation promotes not only IL-7Rα, but also the common γ chain of the receptor and the downstream signaling mediated by pSTAT5. Our results demonstrate a previously unappreciated role of CD27 stimulation as a positive regulator of IL-7Rα during CD8 T-cell responses, provide insights into the mechanistic basis by which CD27 stimulation influences CD8+ T-cell memory differentiation, and highlight the potential of targeting CD27-CD70 axis to enhance IL-7 signaling for antiviral/antitumor immunotherapy.
Quantitative Assessment of Trace‐Element Contamination in Parenteral Nutrition Components
Authors: Olson Logan M. , Wieruszewski Patrick M. , Jannetto Paul J. , Abbott Jillian C. , McMahon M. Molly , Nystrom Erin M. 
Published: June 2019

AbstractBackgroundTrace‐element contamination of contemporary parenteral nutrition (PN) components exists in unknown quantities and, in combination with excessive amounts of certain trace elements provided in commercially available adult, pediatric, and neonatal multitrace‐element (MTE) products, could result in eventual accumulation and toxicity. This study aims to quantify trace‐element contamination in components used for PN compounding to further inform recommendations for MTE product reformulation and individualized trace‐element prescribing in PN.MethodsA total of 32 unique components (65 products) available for PN compounding were tested for manganese, chromium, selenium, zinc, and copper contamination, utilizing inductively coupled plasma mass spectrometry. Theoretical adult, pediatric, and neonatal PNs were formulated to assess the impact of macronutrient and micronutrient component doses on PN trace‐element contamination.ResultsTrace‐element contamination was detected in 24 (75%) components tested. Chromium and manganese were common, present in 65.6% and 51.5% of all components, respectively. Eight components did not contain detectable trace‐element contamination, most notably sterile water, concentrated dextrose, and lipid emulsion. Manganese contamination in theoretical adult, pediatric, and neonatal PN was 25.18, 9.92, and 1.37 µg, respectively. Chromium contamination was 4.85, 1.5, and 0.28 µg, respectively.ConclusionTrace‐element contamination was prevalent in components used to compound PN. Our findings support reformulation of adult, pediatric, and neonatal manufactured MTE products to eliminate chromium, decrease manganese, and supply full daily physiologic requirements of selenium, zinc, and copper. Future study is needed to assess the additional contamination that could occur through the compounding and storage processes.
Exploration of the problems and solutions related to reference introduction prior to calibration of thermal desorber–gas chromatography
Authors: Asfaw Adissu Alemayehu , Van der Veken Matthias , Wolfs Kris , Van Schepdael Ann , Adams Erwin 
Published: June 2019

AbstractReference introduction in thermal desorption with gas chromatography is a critical aspect. It is mostly performed by offline liquid calibration using a micro syringe to inject a liquid standard solution on the sorbent in the thermal desorption tube. This is based on the assumptions that the adsorption‐desorption process is quantitative and that no sample is lost in manipulating the tube. However, for analytical procedures involving thermal extraction of solid matrices, the adsorption‐desorption processes for sample and reference differ and the assumptions are not always fulfilled. This is explored in this work. First, issues related to the online liquid calibration were investigated. With tubes containing only quartz filters, a relative loss of over 80% was noticed for some solvents due to tube manipulation processes. Enclosing a bed of mesoporous silica as sorbent limited the losses to about 25% when samples were immediately analysed, and even better results were obtained when tubes were stored for several hours so that proper adsorption could take place. An additional sweep gas during loading boosted the transfer of analytes with recoveries above 95%. Next, an inline injection system was installed on the thermal desorber instrument. This sorbent free, independent calibration tool avoids the drawbacks of other approaches.
Separation and identification of process‐related substances and degradation products in mycophenolate mofetil by liquid chromatography coupled with quadrupole‐time of flight mass spectrometry
Authors: Lu Yu‐ting , Qi Wen‐zhu , Chen Yan‐fei , Song Min , Hang Tai‐jun 
Published: June 2019

AbstractMycophenolate mofetil is an antiproliferative immunosuppressive agent. Since its clinical efficacy and safety highly depend on the quality, the stability, and impurity profiles of mycophenolate mofetil are paid ever‐increasing attention. However, there are few published studies reporting the complete characterization of both the process‐related substances and degradation products in mycophenolate mofetil. In the present study, a highly specific and efficient liquid chromatography coupled with quadrupole‐time of flight mass spectrometry method was developed for the separation and identification of all the potential impurities in mycophenolate mofetil. According to the ICH Q1A (R2) guideline, the forced degradation studies were conducted to elucidate the stability and degradation pathways of mycophenolate mofetil. A total of 15 related substances, including the process‐related substances and stress degradation products were characterized by the established hyphenated method, 11 of them have not been reported before. In view of the synthetic route and degradation pathways of mycophenolate mofetil, the origins and formation mechanisms of these related substances were discussed. Based on the obtained stability and impurity profiles, key points of the manufacturing process were proposed to deliver mycophenolate mofetil with high purity.
Initial experience of fecal microbiota transplantation in gastrointestinal disease: A case series
Authors: Wang Jiunn‐Wei , Wang Yao‐Kuang , Zhang Faming , Su Yu‐Chung , Wang Jaw‐Yuan , Wu Deng‐Chyang , Hsu Wen‐Hung 
Published: June 2019

AbstractCurrent studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well‐tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier.
Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer
Authors: Zhang Yun‐Kui , Tian Wen‐Ze , Zhang Rong‐Sheng , Zhang Yu‐Jie , Ma Hai‐Tao 
Published: June 2019

AbstractUbiquitin‐specific protease 44 (USP44) has been reported as a tumor suppressor or promoter in some tumors, but its function in non‐small cell lung cancer (NSCLC) is still unclear. In this study, USP44 was found significantly downregulated in both of NSCLC tissues and cell lines, and low expression of USP44 predicted a poor prognosis for NSCLC patients. Overexpression of USP44 markedly downregulated the expression levels of Cyclin D1 and CDK4, but upregulated p53 expression, as a result of which, suppressing the cell growth of NSCLC cells. Further studies indicated that overexpression of USP44 significantly inhibited the phosphorylation of AKT, and its down‐stream signals, including mTOR and P70S6K. Moreover, overexpression of USP44 increased PTEN protein but not its mRNA levels, which suggested that USP44 inhibited AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP44 showed prior evidence of a tumor suppressive function in NSCLC cells, and inhibited NSCLC cell growth by suppressing AKT signaling, suggesting that USP44 could be as a novel target for NSCLC therapy.
A layer potential analysis for transmission problems for Brinkman‐type systems in Lipschitz domains in
Authors: Albişoru Andrei‐Florin 
Published: June 2019

AbstractThe aim of this paper is to establish a well‐posedness result for a boundary value problem of transmission‐type for the standard and generalized Brinkman systems in two Lipschitz domains in , the former being bounded, and the latter, its complement in . As a first step, we establish a well‐posedness result for a transmission problem for the standard Brinkman systems on complementary Lipschitz domains in by making use of the Potential theory developed for such a system. As a second step, we prove our desired result (in L2‐based Sobolev spaces) by using a method based on Fredholm operator theory and the well‐posedness result from the previous step.
Persistent symbiont colonization leads to a maturation of hemocyte response in the Euprymna scolopes/Vibrio fischeri symbiosis
Authors: Rader Bethany , McAnulty Sarah J. , Nyholm Spencer V. 
Published: June 2019

AbstractThe binary association between the squid, Euprymna scolopes, and its symbiont, Vibrio fischeri, serves as a model system to study interactions between beneficial bacteria and the innate immune system. Previous research demonstrated that binding of the squid's immune cells, hemocytes, to V. fischeri is altered if the symbiont is removed from the light organ, suggesting that host colonization alters hemocyte recognition of V. fischeri. To investigate the influence of symbiosis on immune maturation during development, we characterized hemocyte binding and phagocytosis of V. fischeri and nonsymbiotic Vibrio harveyi from symbiotic (sym) and aposymbiotic (apo) juveniles, and wild‐caught and laboratory‐raised sym and apo adults. Our results demonstrate that while light organ colonization by V. fischeri did not alter juvenile hemocyte response, these cells bound a similar number of V. fischeri and V. harveyi yet phagocytosed only V. harveyi. Our results also indicate that long‐term colonization altered the adult hemocyte response to V. fischeri but not V. harveyi. All hemocytes from adult squid, regardless of apo or sym state, both bound and phagocytosed a similar number of V. harveyi while hemocytes from both wild‐caught and sym‐raised adults bound significantly fewer V. fischeri, although more V. fischeri were phagocytosed by hemocytes from wild‐caught animals. In contrast, hemocytes from apo‐raised squid bound similar numbers of both V. fischeri and V. harveyi, although more V. harveyi cells were engulfed, suggesting that blood cells from apo‐raised adults behaved similarly to juvenile hosts. Taken together, these data suggest that persistent colonization by the light organ symbiont is required for hemocytes to differentially bind and phagocytose V. fischeri. The cellular immune system of E. scolopes likely possesses multiple mechanisms at different developmental stages to promote a specific and life‐long interaction with the symbiont.
Mutational Analysis of TYR, OCA2, and SLC45A2 Genes in Chinese Families with Oculocutaneous Albinism
Authors: Lin Ye , Chen Xihui , Yang Ying , Che Fengyu , Zhang Sijia , Yuan Lijuan , Wu Yuanming 
Published: June 2019

AbstractBackgroundOculocutaneous albinism (OCA) is a group of heterogeneous autosomal recessive genetic disorder of melanin synthesis results in hypopigmented hair, skin, and eyes. OCA type 1, OCA type 2, and OCA type 4, which are respectively caused by mutations in TYR, OCA2, and SLC45A2 have high morbidity rates in Asia.MethodsTYR, OCA2, and SLC45A2 mutation analysis was carried out on 18 nonconsanguineous OCA patients and four fetuses were included for prenatal diagnose. Three genes of all individuals were amplified by polymerase chain reaction and examined by Sanger sequencing. The pathogenicity of the detected mutations were analyzed by Mutation Taster, PolyPhen 2, and SIFT software, and the conservation of the substituted amino acids were analyzed by MEGA software.ResultsEleven TYR mutations, three OCA2 mutations, and two SLC45A2 mutations were identified in 14 OCA type 1 patients, two OCA type 2 patients, and two OCA type 4 patients. c.1021A>G, p.R341G in TYR, c.1096_1104del, p.V366*, and c.1079C>T, p.S360F in OCA2 were novel. One of the four fetuses carried compound heterozygous mutation of TYR and became spontaneous abortion, the other three carried no mutations and appeared normal at birth.ConclusionIn this study, specific clinical characteristics of OCA patients were described. Three novel pathogenic mutations were identified which will enrich the mutation spectrum of OCA, and the prenatal genetic screening in fetus at risk of OCA can provide vital information for genetic counseling.
Association of a homozygous GCK missense mutation with mild diabetes
Authors: Marucci Antonella , Biagini Tommaso , Di Paola Rosa , Menzaghi Claudia , Fini Grazia , Castellana Stefano , Cardinale Giuliana Marcella , Mazza Tommaso , Trischitta Vincenzo 
Published: June 2019

AbstractBackgroundHomozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G>C, p.E372D), in a family with one homozygous member showing mild hyperglycemia.MethodsGCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK‐E372D and for previously described homozygous mutations associated with mild (n = 2) or severe (n = 1) hyperglycemia, used as references.ResultsOf four mildly hyperglycemic family‐members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK‐E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p = 0.016) and HbA1c (p = 0.035) correlated with the number of mutated alleles (0–2).In‐silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK‐E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations.ConclusionsWe present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in‐silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations.
Pathogenic missense mutation pattern of forkhead box genes in neurodevelopmental disorders
Authors: Han Lin , Chen Meilin , Wang Yazhe , Wu Huidan , Quan Yingting , Bai Ting , Li Kuokuo , Duan Guiqin , Gao Yan , Hu Zhengmao , Xia Kun , Guo Hui 
Published: June 2019

AbstractBackgroundForkhead box (FOX) proteins are a family of transcription factors. Mutations of three FOX genes, including FOXP1, FOXP2, and FOXG1, have been reported in neurodevelopmental disorders (NDDs). However, due to the lack of site‐specific statistical significance, the pathogenicity of missense mutations of these genes is difficult to determine.MethodsDNA and RNA were extracted from peripheral blood lymphocytes. The mutation was detected by single‐molecule molecular inversion probe‐based targeted sequencing, and the variant was validated by Sanger sequencing. Real‐time quantitative PCR and western blot were performed to assay the expression of the mRNA and protein. To assess the pattern of disorder‐related missense mutations of NDD‐related FOX genes, we manually curated de novo and inherited missense or inframeshift variants within FOXP1, FOXP2, and FOXG1 that co‐segregated with phenotypes in NDDs. All variants were annotated by ANNOVAR.ResultsWe detected a novel de novo missense mutation (NM_001244815: c.G1444A, p.E482K) of FOXP1 in a patient with intellectual disability and severe speech delay. Real‐time PCR and western blot revealed a dramatic reduction of mRNA and protein expression in patient‐derived lymphocytes, indicating a loss‐of‐function mechanism. We observed that the majority of the de novo or transmitted missense variants were located in the FOX domains, and 95% were classified as pathogenic mutations. However, 10 variants were located outside of the FOX domain and were classified as likely pathogenic or variants of uncertain significance.ConclusionOur study shows the pathogenicity of missense and inframeshift variants of NDD‐related FOX genes, which is important for clinical diagnosis and genetic counseling. Functional analysis is needed to determine the pathogenicity of the variants with uncertain clinical significance.
High‐efficiency cross and linear‐to‐circular polarization converters based on novel frequency selective surfaces
Authors: Wang Zhenglong , Ge Yuehe , Lin Chengxiu , Liu Kaiting , Pu Jixiong 
Published: June 2019

AbstractMost high‐efficiency polarization converters in literatures are based on reflective structures. Here we report the designs and experiments of high‐efficiency transmissive polarization converters using novel compact frequency‐selective surfaces (FSSs). By combining the common dipole and square ring based band‐pass FSSs, a novel FSS can be generated, whose high‐efficiency pass bands and transmissive phases for two orthogonal polarizations can be tuned by changing the dimensions of the FSS structure. As demonstrations of the concept, a transmissive cross polarization converter (a half‐wave plate) and a transmissive linear‐to‐circular polarization (LP‐CP) converter (a quarter‐wave plate) are designed and tested, respectively. Simulated results show that the polarization conversion ratio over 90% for the transmissive cross‐polarization converter is from 18.5 to 23.5 GHz, about 23.8%, and the 3‐dB LP‐CP conversion bandwidth is 19.6%. Experiments are carried out to validate both designs.
Reconstruction of the 12‐lead ECG using a novel MR‐compatible ECG sensor network
Authors: Dos Reis Jesús E. , Soullié Paul , Oster Julien , Palmero Soler Ernesto , Petitmangin Gregory , Felblinger Jacques , Odille Freddy 
Published: June 2019

PurposeCurrent electrocardiography (ECG) devices in MRI use non‐conventional electrode placement, have a narrow bandwidth, and suffer from signal distortions including magnetohydrodynamic (MHD) effects and gradient‐induced artifacts. In this work a system is proposed to obtain a high‐quality 12‐lead ECG.MethodsA network of N electrically independent MR‐compatible ECG sensors was developed (N = 4 in this study). Each sensor uses a safe technology – short cables, preamplification/digitization close to the patient, and optical transmission – and provides three bipolar voltage leads. A matrix combination is applied to reconstruct a 12‐lead ECG from the raw network signals. A subject‐specific calibration is performed to identify the matrix coefficients, maximizing the similarity with a true 12‐lead ECG, acquired with a conventional 12‐lead device outside the scan room. The sensor network was subjected to radiofrequency heating phantom tests at 3T. It was then tested in four subjects, both at 1.5T and 3T.ResultsRadiofrequency heating at 3T was within the MR‐compatibility standards. The reconstructed 12‐lead ECG showed minimal MHD artifacts and its morphology compared well with that of the true 12‐lead ECG, as measured by correlation coefficients above 93% (respectively, 84%) for the QRS complex shape during steady‐state free precession (SSFP) imaging at 1.5T (respectively, 3T).ConclusionHigh‐quality 12‐lead ECG can be reconstructed by the proposed sensor network at 1.5T and 3T with reduced MHD artifacts compared to previous systems. The system might help improve patient monitoring and triggering and might also be of interest for interventional MRI and advanced cardiac MR applications.
On a new exponential iterative method for solving nonsmooth equations
Authors: Śmietański Marek J. 
Published: June 2019

SummaryIn this paper, we propose a new distinctive version of a generalized Newton method for solving nonsmooth equations. The iterative formula is not the classic Newton type, but an exponential one. Moreover, it uses matrices from B‐differential instead of generalized Jacobian. We prove local convergence of the method and we present some numerical examples.