bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of cystatin SN promotes hepatocellular carcinoma progression and predicts a poor prognosis
Authors: Cui Yifeng , Sun Dan , Song Ruipeng , Zhang Shugeng , Liu Xirui , Wang Yan , Meng Fanzheng , Lan Yaliang , Han Jihua , Pan Shangha , Liang Shuhang , Zhang Bo , Guo Hongrui , Liu Yufeng , Lu Zhaoyang , Liu Lianxin 
Published: May 2019

AbstractCystatin SN, a specific cysteine protease inhibitor, is thought to be involved in various malignant tumors. Therefore, we evaluated the role of cystatin SN in hepatocellular carcinoma (HCC). Notably, cystatin SN was elevated in tumorous samples and cells. Moreover, overexpression of cystatin SN was correlated with tumor diameter and TNM stage. Cox multivariate analysis displayed that cystatin SN was an independent prognosis indicator and that high cystatin SN level was associated with a dismal prognosis. Moreover, cystatin SN enhancement facilitated the proliferation, migratory, and invasive potential of Huh7 and HCCLM3 cells, whereas cystatin SN knockdown caused the opposite effect. Cystatin SN also modulated the epithelial‐mesenchymal transition progression through the PI3K/AKT pathway. In vivo cystatin SN promoted HCCLM3 cell growth and metastasis in xenograft mice model. Thus, cystatin SN was involved in HCC progression and could be a latent target for HCC treatment.
Quantitative Comparison of the Efficacies of 5 First‐Line Drugs for Primary Restless Leg Syndrome
Authors: Zhang Ningyuan , Li Yunfei , Lv Yinghua , Xu Ling , Chen Junchao , Liu Hongxia , Li Lujin , Zheng Qingshan 
Published: May 2019

AbstractComparative analyses of the efficacies of dopaminergic agonists (pramipexole, ropinirole, and rotigotine patch) and α‐2‐δ ligands (gabapentin enacarbil and pregabalin) for treatment of primary restless leg syndrome (RLS) are lacking because of the few head‐to‐head clinical trials. A model‐based meta‐analysis approach was employed to quantitatively compare the efficacies of these 5 first‐line RLS drugs. Longitudinal efficacy data of RLS drugs were collected from published eligible literature. Mean changes in both the International Restless Leg Syndrome Study Group (IRLS) rating scale and Clinical Global Impression Improvement (CGI‐I) scale response rate were analyzed. A study‐level population pharmacodynamic model was used to fit the dose‐effect relationship and to describe the therapeutic effect over time for RLS drugs and placebo, and the typical efficacies of these drugs were compared. The onset of action was rapid for RLS drugs. In the placebo group, typical maximum IRLS reduction (Emax,IRLS) and CGI‐I response rate (Emax,CGI‐I) were –9.34 points and 48.2%, respectively. After deducting placebo effects, we found that the baseline IRLS score was significantly correlated with the Emax,IRLS of dopaminergic agonists. Typical Emax,IRLS of dopaminergic agonists was expressed as points. Typical Emax,IRLS values of pregabalin and gabapentin enacarbil were –5.95 points and –4.00 points, respectively. The therapeutic effect of dopaminergic agonists was found to be associated with baseline symptom severity. In RLS patients with more severe symptoms, the therapeutic effect of dopaminergic agonists tended to be better than that of α‐2‐δ ligands.
Palynological investigation of lactiferous flora (Apocynaceae) of District Rawalpindi, Pakistan, using light and scanning electron microscopy
Authors: Naz Saeeda , Zafar Muhammad , Ahmad Mushtaq , Memon Rabia A. , Sultana Shazia , Bahadur Saraj , Ozdemir Fethi A. , Siddiq Zafar , Shah Muhammad A. 
Published: May 2019

AbstractThis was the first comprehensive pollen micromorphological investigation of lactiferous flora (Apocynaceae) of District Rawalpindi, Pakistan. The pollen morphology of 10 species of the family Apocynaceae was observed and documented using light microscopy and scanning electron microscopy. Pollen was found subspheroidal in shape in most of the species, however peroblate shape was noted in Vinca major. Exine sculpturing patterns (psilate, rugulate, scabrate, and microreticulate) were observed. The result indicated that exine ornamentation of Apocynaceae taxa is systematically informative at generic and species levels. Most of the species have tricolporate type pollen but tetraporate pollen was also observed in Trachelospermum jasminoides and tetracolpate in V. major. Minimum equatorial diameter was noted in Carissa edulis (27.13 μm) and maximum in V. major (108.25 μm). Similarly, maximum exine thickness was found in Cascabela thevetia (9.5 μm). In the present findings, the pollen morphological data are compared with available other pollen studies to evaluate the taxonomic value of pollen traits in Apocynaceae taxa by using multiple microscopic techniques. Furthermore, molecular and phylogenetic studies were recommended to strengthen the systematics of Apocynaceae taxa.
Mechanisms of natural killer cell-mediated cellular cytotoxicity
Authors: Prager Isabel , Watzl Carsten 
Published: May 2019

Abstract
Cellular cytotoxicity, the ability to kill other cells, is an important effector mechanism of the immune system to combat viral infections and cancer. Cytotoxic T cells and natural killer (NK) cells are the major mediators of this activity. Here, we summarize the cytotoxic mechanisms of NK cells. NK cells can kill virally infected of transformed cells via the directed release of lytic granules or by inducing death receptor-mediated apoptosis via the expression of Fas ligand or TRAIL. The biogenesis of perforin and granzymes, the major components of lytic granules, is a highly regulated process to prevent damage during the synthesis of these cytotoxic molecules. Additionally, NK cells have developed several strategies to protect themselves from the cytotoxic activity of granular content upon degranulation. While granule-mediated apoptosis is a fast process, death receptor-mediated cytotoxicity requires more time. Current data suggest that these 2 cytotoxic mechanisms are regulated during the serial killing activity of NK cells. As many modern approaches of cancer immunotherapy rely on cellular cytotoxicity for their effectiveness, unraveling these pathways will be important to further progress these therapeutic strategies.
Effects of Intradiscal Injection of Local Anesthetics on Intervertebral Disc Degeneration in Rabbit Degenerated Intervertebral Disc
Authors: Ura Katsuro , Sudo Hideki , Iwasaki Koji , Tsujimoto Takeru , Ukeba Daisuke , Iwasaki Norimasa 
Published: May 2019

ABSTRACTAnalgesic discoblock is widely used for the diagnosis or treatment of discogenic low back pain by injecting local anesthetics. The purpose of this study was to investigate the deleterious effects of local anesthetics on degenerated rabbit intervertebral disks (IVDs) using an organotypic culture model and in vivo long‐term follow‐up model. To induce IVD degeneration, a rabbit annular puncture model was used. For the organotypic culture model, degenerated IVDs were harvested 1 month after the initial annular puncture and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine and 0.5% bupivacaine). To perform in vivo analysis, local anesthetics were injected into degenerated IVDs, and IVDs were prepared for histological analysis after 6 or 12 months. In the organotypic model, terminal deoxynucleotidyl transferase dUTP nick end labeling‐positive nucleus pulposus (NP) cells were significantly increased in the bupivacaine group compared with the other groups. In the in vivo study, the number of NP cells was significantly decreased in the saline and local anesthetics groups compared with the untreated control and puncture‐only groups. However, there was no significant difference among the saline, lidocaine, and bupivacaine groups. In addition, histological analysis showed no significant difference of IVD degeneration among the puncture‐only, saline, lidocaine, and bupivacaine groups. Although bupivacaine induced apoptotic NP cell death in the organotypic culture model, in vivo observations did not show any definitive proof to suggest that local anesthetics were capable of promoting degeneration in the degenerated IVD, except for pressurized injection‐induced damage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1963–1971, 2019
No Evidence of Systemic Inflammation in Symptomatic Patients With Femoroacetabular Impingement
Authors: Talks Benjamin J. , Fernquest Scott , Palmer Antony , Broomfield John , Pattinson Kyle , Bradwell Arthur , Glyn‐Jones Siôn 
Published: May 2019

ABSTRACTFemoroacetabular impingement (FAI) is a common cause of hip pain and represents a major cause of early osteoarthritis. The role of systemic inflammation in pre‐arthritic hip conditions remains largely unknown and uninvestigated. Serum‐free light chains (sFLCs) are inflammatory markers produced by B cells. This study aimed to determine whether there was evidence of systemic inflammation in patients with FAI, defined by sFLCs, and whether this correlated with markers of disease severity. Participants for this study were recruited from a single center (Nuffield Orthopedic Center, Oxford) and were taking part in the Femoroacetabular Impingement Trial. The cohort comprised 115 individuals (38 male, 77 female, mean age 37 years): 57 individuals received surgical intervention and 58 received physiotherapy. All individuals provided patient‐reported outcome measures and serum samples at baseline and follow‐up 8 months post‐randomization. sFLC concentrations were measured in serum samples by immunoturbidimetry. At baseline, for all individuals, mean polyclonal sFLC concentrations were 30.36 mg/l (standard deviation [SD] 9.23). At follow‐up, the mean polyclonal sFLC concentrations were 31.68 mg/l (SD 9.61) in the surgical intervention cohort, and 29.48 mg/l (SD 7.85) in the physiotherapy intervention cohort. There was no significant correlation between sFLC concentrations and any of the patient reported outcome measures, or radiographic measures: average or maximum alpha angle, or center edge angle. In conclusion, in patients with symptomatic FAI there was no systemic inflammation, as defined by sFLC concentrations, and no correlation between sFLC concentrations and measures of disease severity. The lack of inflammation suggests FAI is a mechanical phenomenon. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2189–2196, 2019
A robust LC–MS/MS assay with online cleanup for measurement of serum testosterone
Authors: Zhou Yu , Wang Sihe 
Published: May 2019

AbstractAccurate measurement of low levels of testosterone is critical for diagnosis and treatment of androgen disorders. The very low concentrations of testosterone in children, females, and males with androgen suppression therapies necessitate the use of mass spectrometry‐based methods. We aimed to develop a liquid chromatography with tandem mass spectrometry method with simplified sample preparation and online solid‐phase extraction cleanup to achieve enhanced precision, accuracy, robustness, and cost‐effectiveness. The assay was linear from 10 to 20 000 pg/mL with an analytical recovery of 93–104%. The total coefficient of variation was 2.5, 1.9, and 1.7% at concentration levels of 348, 5432, and 10 848 pg/mL, respectively. No significant carryover was observed from samples with concentrations up to 20 000 pg/mL. No significant interference was observed from androstenedione, dehydroepiandrosterone, epi‐testosterone, and estriol. Comparison with CDC Hormone Standardization program (HoSt) reference samples with defined values (n = 40) showed a Deming regression slope of 0.963, intercept of 28.06 pg/mL, standard error of estimate was 66.9, a correlation coefficient of 0.9996, and a mean bias of −0.6%. The method met the accuracy criteria by the CDC HoSt program. In addition, we achieved >12 000 injections on a single analytical column without significant performance deterioration due to the specific online solid‐phase extraction settings.
Application of high‐surface‐area graphitized carbon black with primary secondary amine as an alternative quick, easy, cheap, effective, rugged, and safe cleanup material for pesticide multi‐residue analysis in spinach
Authors: Islam Abul Kasem Mohammad Mydul , Lee Hyo‐Sub , Ro Jin‐Ho , Kim Danbi , Kwon Hyeyoung 
Published: May 2019

AbstractA multi‐residue method has been developed and validated to determine 46 pesticides in spinach using liquid chromatography tandem mass spectrometry. The method is based on modified quick, easy, cheap, effective, rugged, and safe sample preparation, where high‐surface‐area graphitized carbon black was used first as sorbent material in the dispersive solid‐phase extraction. The method was compared with the quick, easy, cheap, effective, rugged, and safe method. The morphology, surface area, pore size, and pore volume of the sorbent was determined. The results obtained show that the sorbent consists of high surface area (233 m2/g) and large pore volume (1.5 cm3/g). The calibration curve correlation coefficient (R2) of the method was at least 0.99. The average recoveries ranged from 74 to 116%, and limits of detection and quantification from 0.0001 to 0.002 mg/kg and from 0.0002 to 0.005 mg/kg, respectively. Using the method, the pesticides exhibited low matrix effect (< 20%), except for nicosulfuron (29.86%), methomyl (26.77%), and flufenoxuron (24.65%). The method showed better potential to remove pigments than the quick, easy, cheap, effective, rugged, and safe method. It is demonstrated that the proposed method could be useful alternative for sample preparation of spinach and other matrices in future.
Diagnostic performance of circular RNAs in human cancers: A systematic review and meta‐analysis
Authors: Li Juan , Li Hang , Lv Xiaoting , Yang Zitai , Gao Min , Bi Yanhong , Zhang Ziwei , Wang Shengli , Cui Zhigang , Zhou Baosen , Yin Zhihua 
Published: May 2019

AbstractBackgroundRecently, accumulating evidence have revealed that circular RNA (circRNA) was deregulated in multiple types of cancer, suggesting that circRNA might serve as a novel candidate biomarker of cancer diagnosis. However, inconsistent results have become an obstacle in applying circRNAs to clinical practice. The aim of this study is to evaluate diagnostic value of circRNAs among cancers.MethodsA literature search was systematically performed among PubMed, Sciencedirect, Cochrane Library, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure databases up to February 15, 2019. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratios, negative likelihood ratios, diagnostic odds ratio, and area under the SROC curve (AUC) were applied to evaluate diagnostic performance of circRNAs.ResultsIn total, the study included 64 studies with single circRNA and 13 studies with combined circRNAs. Overall, the study presented that a single circRNA had moderate diagnostic value, with a SEN of 0.75, a SPE of 0.76, and an AUC of 0.82. The plasma circRNAs had higher diagnostic accuracy than tissue (AUC: 0.87, 95% confidence interval [CI]: 0.83–0.89 for plasma/serum subgroup; AUC: 0.79, 95% CI: 0.75–0.82 for tissue subgroup). Furthermore, the combined circRNAs had good diagnostic efficacy for GC, with a SEN of 0.89, a SPE of 0.94, and an AUC of 0.97, respectively.ConclusionThis study confirmed that circRNAs may be candidate biomarkers for cancer diagnosis. In particular, diagnosis of combined circRNAs will be a new alternative applied to clinical research and practice for cancer.
A depth encoding PET detector using four‐crystals‐to‐one‐SiPM coupling and light‐sharing window method
Authors: Zhang Xi , Xie Siwei , Yang Jingwu , Weng Fenghua , Xu Jianfeng , Huang Qiu , Peng Qiyu 
Published: May 2019

PurposeDepth of interaction (DOI) decoding capability is of great importance for positron emission tomography (PET) requiring high resolution. In this study, we presented a novel low‐cost DOI detector design with four crystals coupling to one SiPM, based on the method of rectangular light‐sharing window (RLSW). A prototype detector was constructed, calibrated, and assessed using the methods of homogeneous radiation and flood map analysis.MethodsThe DOI detector was constructed with a 4 × 4 array of lutetium‐yttrium oxyorthosilicate (LYSO) crystals (2.95 mm × 2.95 mm × 20 mm3), barium sulfate (BaSO4) reflectors, and optical glues. A RLSW 7 mm in height was deployed in the BaSO4 reflectors. A non‐DOI detector with identical dimensions and without RLSW was also constructed for comparison. The light‐output surface of the detector was air‐coupled with a 4 × 4 array of SiPMs (3 mm × 3 mm2). The signals generated from the 16 SiPMs were read out by a custom‐designed electronic system, and the signals from four adjacent 3 mm SiPMs were summed into one signal to emulate a 2 × 2 array of 6 mm SiPMs. The RLSW caused the DOI‐related position shifts of the crystal spots in the flood map. A homogeneous radiation method was used to establish the transfer functions to convert the spot shifts measured from the flood map into DOI measurements. The accuracy of the DOI measurements was assessed with data acquired using the conventional collimated radiation method.ResultsAll 16 crystals are distinctly separated from each other in the flood map. Twelve crystals, including four central crystals and eight edge crystals, have the DOI capability. The full width half maximum (FWHM) of the DOI measurements of the central crystals and the edge crystals are 3.06 ± 0.08 and 3.79 ± 0.15 mm, respectively, for the configuration with four crystals coupling to one SiPM. By contrast, the FWHMs (3.98 ± 0.16 and 5.12 ± 0.38 mm, respectively) are slightly worse for the configuration with one crystal coupling to one SiPM. The average and standard deviation (STD) of the FWHM energy resolutions of the DOI detector and non‐DOI detector were 10.2% ± 0.7% and 10.7% ± 1.7%, respectively. Their FWHM coincidence timing resolutions were 197.0 ± 9.6 and 206.4 ± 13.3 ps, respectively. The RLSW had no significant impact on the energy resolutions and timing resolutions of the DOI detector.ConclusionsThe novel four‐crystals‐to‐one‐SiPM coupling technology is a cost‐efficient approach to construct high‐performance detector modules with DOI capability. The methods of homogeneous radiation and flood map analysis are easy to perform and of good performance. Those methods can be adapted in the clinic PET scanners to enable the capability of DOI measurements.
Assessing the modulation of cutaneous sensory fiber excitability using a fast perception threshold tracking technique
Authors: Nielson Hoberg Tatiana , Frahm Steffen , Hennings Kristian , Arendt‐Nielsen Lars , Dahl Mørch Carsten 
Published: May 2019

AbstractIntroductionTopical application of lidocaine‐and‐prilocaine (LP) cream attenuates the functionality of small cutaneous nerve fibers. The aim of this human study was to measure the underlying excitability modulation of small cutaneous nerve fibers using a novel and fast perception threshold tracking (PTT) technique.MethodsSmall sensory fibers were selectively blocked by 120‐minute topical application of LP and confirmed by quantitative sensory testing. Excitability changes of small (activated by a specially designed pin electrode) and large (patch electrode) nerve fibers were assessed as the strength–duration relation and threshold electrotonus.ResultsThe excitability assessed by the strength–duration relation and threshold electrotonus was significantly modulated for the small afferents (P < 0.05, Wilcoxon's test) but not the large afferents.DiscussionThis novel PTT technique was able to assess inhibition of membrane properties of small cutaneous fibers, suggesting the usefulness of the technique as a diagnostic method for assessing impairment of small fibers, as seen in many types of polyneuropathies.
Investigation of the psychometric properties of the inclusion body myositis functional rating scale with rasch analysis
Authors: Ramdharry Gita , Morrow Jasper , Hudgens Stacie , Skorupinska Iwona , Gwathmey Kelly , Currence Melissa , Herbelin Laura , Jawdat Omar , Pasnoor Mamatha , Mcvey April , Barohn Richard J. , Burns Ted M. , Dimachkie Mazen M. , Amato Anthony A. , Hanna Michael G. , Machado Pedro M. 
Published: May 2019

ABSTRACTIntroductionThe Inclusion Body Myositis Functional Rating Scale (IBMRFS) is a 10‐item clinician‐rated ordinal scale developed for people with inclusion body myositis.MethodsSingle observations of the IBMFRS were collected from 132 patients. After Rasch analysis, modifications were made to the scale to optimize fit to the Rasch model while maintaining clinical validity and utility.ResultsThe original IBMFRS did not fit the assumptions of the Rasch model because of multidimensionality of the scale. Items assessed local dependence, disordered step thresholds, and differential item functioning. Deconstructing the scale into upper limb (IBMFRS‐UL) and lower limb (IBMFRS‐LL) scales improved fit to the Rasch model. A 9‐item scale with the swallowing item removed (IBMFRS‐9) remained multidimensional but demonstrated the ability to discriminate patients along the severity continuum. IBMFRS‐UL, IBMFRS‐LL, and IBMFRS‐9 scores were transformed to a 0–100 scale for comparability.DiscussionThis analysis has led to the development of 3 optimized versions of the IBMFRS. Muscle Nerve 60: 161–168, 2019
First‐in‐human implantation of a mid‐field powered neurostimulator at the sacral nerve: Results from an acute study
Authors: van Kerrebroeck Philip E. V. A. , Reekmans Mathias , van Koeveringe Gommert A. , Yeh Alexander J. , Fayram Timothy A. , Sharan Ashwini D. , Comiter Craig V. 
Published: May 2019

AbstractIntroductionCommercially approved implantable systems for sacral neuromodulation require the implantation of a multipolar lead subcutaneously connected to an implantable pulse generator (IPG). Eliminating the need for an IPG would eliminate the need for tunneling of the lead, reduce procedure time, infection risk, and the need for IPG replacement. The objective was to demonstrate the feasibility of implanting the AHLeveeS System in the S3 Foramen to stimulate the S3 sacral nerve.Materials and MethodsA first‐in‐human, prospective, single center, nonrandomized, acute feasibility clinical investigation at the Maastricht University Medical Center+. Patients with refractory overactive bladder underwent acute implantation of the AHLeveeS neurostimulator before the InterStim procedure. Outcome measurements included motor responses, procedural time and a scoring of the difficulty of the implant and explant procedure. Retrospectively, qualitative responses to the stimulation protocol were assessed by video motion analyses. Only descriptive statistics were used.ResultsDuring the stimulation a motor response to stimulation was seen in four of the five subjects. In all implantations the AHLeveeS was correctly placed. The median time for complete procedure was 24 minutes. The implant and explant procedures were successfully performed and no device or procedure related adverse events occurred.ConclusionsThe results from this acute first‐in‐human study demonstrate the feasibility of implantation and acute stimulation of the sacral nerve with this mid‐field powered system. Future clinical studies will focus on safety and efficacy of a chronically implanted device.