bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro and in vivo studies reveal α-Mangostin, a xanthonoid from Garcinia mangostana, as a promising natural antiviral compound against chikungunya virus
Authors: Patil Poonam , Agrawal Megha , Almelkar Shahdab , Jeengar Manish Kumar , More Ashwini , Alagarasu Kalichamy , Kumar Naveen V. , Mainkar Prathama S. , Parashar Deepti , Cherian Sarah 
Published: February 2021

AbstractBackgroundChikungunya virus (CHIKV), a serious health problem in several tropical countries, is the causative agent of chikungunya fever. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. As diverse natural phenolic compounds have been shown to possess antiviral activities, we explored the antiviral activity of α-Mangostin, a xanthanoid, against CHIKV infection.MethodsThe in vitro prophylactic and therapeutic effects of α-Mangostin on CHIKV replication in Vero E6 cells were investigated by administering it under pre, post and cotreatment conditions. The antiviral activity was determined by foci forming unit assay, quantitative RT-PCR and cell-based immune-fluorescence assay. The molecular mechanism of inhibitory action was further proposed using in silico molecular docking studies.ResultsIn vitro studies revealed that 8 µM α-Mangostin completely inhibited CHIKV infectivity under the cotreatment condition. CHIKV replication was also inhibited in virus-infected mice. This is the first in vivo study which clearly showed that α-Mangostin is effective in vivo by significantly reducing virus replication in serum and muscles. Molecular docking indicated that α-Mangostin can efficiently interact with the E2–E1 heterodimeric glycoprotein and the ADP-ribose binding cavity of the nsP3 macrodomain.ConclusionsThe findings suggest that α-Mangostin can inhibit CHIKV infection and replication through possible interaction with multiple CHIKV target proteins and might act as a prophylactic/therapeutic agent against CHIKV.
Real-time sensing of neurotransmitters by functionalized nanopores embedded in a single live cell
Authors: Zhang Xialin , Dou Linqin , Zhang Ming , Wang Yu , Jiang Xin , Li Xinqiong , Wei Long , Chen Yuejia , Zhou Cuisong , Geng Jia 
Published: February 2021

AbstractInterface between neuron cells and biomaterials is the key to real-time sensing, transmitting and manipulating of neuron activities, which are the long-term pursue of scientists and gain intense research focus recently. It is of great interest to develop a sensor with exquisite sensitivity and excellent selectivity for real-time monitoring neurotransmitters transport through single live cell. Sensing techniques including electrode-based methods, optogenetics, and nanowire cell penetration systems have been developed to monitor the neuron activities. However, their biocompatibilities remain a challenge. Protein nanopores with membrane compatibility and lumen tunability provide real-time, single-molecule sensitivities for biosensing of DNA, RNA, peptides and small molecules. In this study, an engineered protein nanopore MspA (Mycobacterium smegmatis porin A) through site-directed mutation with histidine selectively bind with Cu2+ in its internal lumen. Chelation of neurotransmitters such as L-glutamate (L-Glu), dopamine (DA) and norepinephrine (NE) with the Cu2+ creates specific current signals, showing different transient current blockade and dwell time in single channel electrophysiological recording. Furthermore, the functionalized M2MspA-N91H nanopores have been embedded in live HEK293T cell membrane for real-time, in situ monitoring of extracellular L-glutamate translocating through the nanopore. This biomimetic neurotransmitter nanopore has provided a new platform for future development of neuron sensors, drug carrier and artificial synapse.
Pregnancy Serum DLK1 Concentrations Are Associated With Indices of Insulin Resistance and Secretion
Authors: Petry Clive J , Burling Keith A , Barker Peter , Hughes Ieuan A , Ong Ken K , Dunger David B 
Published: February 2021

AbstractContextDelta like noncanonical notch ligand 1 (DLK1) is a paternally expressed imprinted gene that encodes an epidermal growth factor repeat-containing transmembrane protein. A bioactive, truncated DLK1 protein is present in the circulation and has roles in development and metabolism.ObjectiveWe sought to investigate links between maternal pregnancy circulating DLK1 concentrations and: (1) maternal and fetal DLK1 genotypes, (2) maternal insulin resistance and secretion, and (3) offspring size at birth.Patients, design, and settingWe measured third-trimester maternal serum DLK1 concentrations and examined their associations with parentally transmitted fetal and maternal DLK1 genotypes, indices of maternal insulin resistance and secretion derived from 75-g oral glucose tolerance tests performed around week 28 of pregnancy, and offspring size at birth in 613 pregnancies from the Cambridge Baby Growth Study.ResultsMaternal DLK1 concentrations were associated with the paternally transmitted fetal DLK1 rs12147008 allele (P = 7.8 × 10-3) but not with maternal rs12147008 genotype (P = 0.4). Maternal DLK1 concentrations were positively associated with maternal prepregnancy body mass index (P = 3.5 × 10-6), and (after adjustment for maternal body mass index) with both maternal fasting insulin resistance (Homeostatic Model Assessment of Insulin Resistance: P = 0.01) and measures of maternal insulin secretion in response to oral glucose (insulinogenic index: P = 1.2 × 10-3; insulin disposition index: P = 0.049). Further positive associations were found with offspring weight (P = 0.02) and head circumference at birth (P = 0.04).ConclusionThese results are consistent with a partial paternal or placental origin for the maternal circulating DLK1 which may lead to increased maternal circulating DLK1 concentrations, stimulation of maternal insulin resistance and compensatory hyperinsulinemia during pregnancy, and the promotion of fetal growth.
An Unanticipated Role for Sphingosine Kinase-2 in Bone and in the Anabolic Effect of Parathyroid Hormone
Authors: Walker Joanne M , Yao Gang-Qing , Siu Edwin , Zhu Meiling , Sun Ben-hua , Simpson Christine , Insogna Karl L 
Published: February 2021

Abstract
Sphingosine-1-phosphate (S1P) is an anabolic clastokine. Sphingosine kinase (SPHK) is the rate-limiting enzyme in S1P production and has 2 isoforms. To evaluate the roles of SPHK1 and SPHK2 in bone, we examined the skeletal phenotype of mice with selective deletion of SPHK1 in osteoclasts (SPHK1-Oc−/−) and mice in which the SPHK2 gene was deleted in all tissues (SPHK2−/−). SPHK1-Oc−/− had normal bone mass. By contrast, SPHK2−/− female mice had a 14% lower spinal bone mineral density (BMD; P &lt; 0.01) and males a 22% lower BMD at the same site (P &lt; 0.001). SPHK2−/− and control mice were subsequently treated either with daily parathyroid hormone [PTH](1-34) or vehicle for 29 days. The response to PTH was significantly attenuated in the SPHK2−/−mice. The mean femoral bone volume to total volume fraction (BV/TV) increased by 24.8% in the PTH-treated female control animals vs 10.6% in the vehicle-treated female controls (P &lt; 0.01). In contrast, in the SPHK2−/− female mice the difference in femoral trabecular BV/TV at the end of treatment was not significant (20.5 vs13.3%, PTH vs vehicle, P = NS). The anabolic response to PTH was significantly attenuated in the spine of male SPHK2−/− mice (29.7% vs 23.1%, PTH vs vehicle, in controls, P &lt; 0.05; 26.9% vs 19.5% PTH vs vehicle in SPHK2−/− mice, P = NS). The spine responded normally in the SPHK2−/− female mice. Interestingly, suppression of sclerostin was blunted in the SPHK2−/− mice when those animals were treated with an anabolic PTH regimen. We conclude that SPHK2 has an important role in mediating both normal bone remodeling and the anabolic response to PTH.
Parathyroid Hormone Induces Transition of Myofibroblasts in Arteriovenous Fistula and Increases Maturation Failure
Authors: Liu Chung-Te , Hsu Shih-Chang , Hsieh Hui-Ling , Chen Cheng-Hsien , Chen Chun-You , Sue Yuh-Mou , Lin Feng-Yen , Shih Chun-Ming , Shiu Yan-Ting , Huang Po-Hsun 
Published: February 2021

Abstract

Context
Arteriovenous fistula (AVF) maturation failure remains a clinical dilemma, and its pathobiology is largely unclear. Secondary hyperparathyroidism is a complication of chronic renal failure that is associated with cardiovascular disease. While parathyroid hormone (PTH) has a prosclerotic effect on vascular smooth muscle cells (VSMCs), its role in AVF maturation failure remained unknown.

Objective
This work aimed to investigate the association between plasma PTH and AVF maturation.

Methods
Patients receiving AVF creation were enrolled retrospectively. A mouse model of secondary hyperparathyroidism and aortocaval AVF was used to investigate the effect of PTH on an AVF lesion. A cell model of VSMCs treated with PTH in a pressurized culture system was used to disclose the signaling pathway underlying the effect of PTH on an AVF lesion.

Results
In patients receiving AVF creation, higher PTH was associated with an increased risk for maturation failure. In a mouse model, vascular wall thickness and myofibroblasts of AVF significantly increased with higher PTH. When the same mice were treated with cinacalcet, AVF lesions were attenuated by suppression of PTH. A cell model showed that PTH increased the marker of myofibroblasts, integrin β6 subunit (ITGB6), via the phosphorylated protein kinase B pathway. Finally, in the same model of mice AVF, higher PTH also increased the expression of ITGB6 in the smooth muscle layer of AVF, suggesting the transition to myofibroblast.

Conclusion
Overall, our results suggest that higher PTH increased the risk of AVF maturation failure through increasing the transition of VSMCs to myofibroblasts. Lowering PTH may be a strategy to enhance AVF maturation.
Surgical management of symptomatic osteonecrosis and utility of core decompression of the femoral head in young people with acute lymphoblastic leukaemia recruited into UKALL 2003
Authors: Amin Nadia , Kraft Jeannette , Fishlock Adelle , White Alan , Holton Colin , Kinsey Sally , Feltbower Richard , James Beki 
Published: February 2021

AimsOsteonecrosis (ON) can cause considerable morbidity in young people who undergo treatment for acute lymphoblastic leukaemia (ALL). The aims of this study were to determine the operations undertaken for ON in this population in the UK, along with the timing of these operations and any sequential procedures that are used in different joints. We also explored the outcomes of those patients treated by core decompression (CD), and compared this with conservative management, in both the pre- or post-collapse stages of ON.MethodsUK treatment centres were contacted to obtain details regarding surgical interventions and long-term outcomes for patients who were treated for ALL and who developed ON in UKALL 2003 (the national leukaemia study which recruited patients aged 1 to 24 years at diagnosis of ALL between 2003 and 2011). Imaging of patients with ON affecting the femoral head was requested and was used to score all lesions, with subsequent imaging used to determine the final grade. Kaplan-Meier failure time plots were used to compare the use of CD with non surgical management.ResultsDetailed information was received for 85 patients who had developed ON during the course of their ALL treatment. A total of 206 joints were affected by ON. Of all joints affected by ON, 21% required arthroplasty, and 43% of all hips affected went on to be replaced. CD was performed in 30% of hips affected by ON. The majority of the hips were grade 4 or 5 at initial diagnosis of ON. There was no significant difference in time to joint collapse between those joints in which CD was performed, compared with no joint-preserving surgical intervention.ConclusionThere is a high incidence of surgery in young people who have received treatment for ALL and who have developed ON. Our results suggest that CD of the femoral head in this group of patients does not delay or improve the rates of femoral head survival. Cite this article: Bone Joint J 2021;103-B(3):589–596.
Does total hip arthroplasty have a higher risk of failure in patients who undergo lumbar spinal fusion?
Authors: Di Martino Alberto , Bordini Barbara , Ancarani Cristina , Viceconti Marco , Faldini Cesare 
Published: February 2021

Aims Total hip arthroplasty (THA) patients undergoing or having a prior lumbar spine fusion (LSF) have an increased risk of mechanical complications. The aim of this registry-based, retrospective comparative cohort study is to assess the longer term survival of THA in patients who have undergone a LSF during a 17-year period (2000 to 2017). Methods A registry-based population study was conducted on 679 patients who underwent both THA and LSF surgeries. Patients were identified from the regional arthroplasty data base and cross linked to patients with LSF from the regional hospital discharge database between 2000 and 2017. Demographic data, diagnosis leading to primary THA, primary implant survival, perioperative complications, number and causes of failure, and patients requiring revision arthroplasty were collated and compared. For comparison, data from 67,919 primary THAs performed during the same time time period were also retrieved and analyzed. Results Patients undergoing THA and LSF showed homogeneous demographic data compared to those undergoing THA alone, but a significantly lower eight-year THA implant survival (96.7 vs 96.0, p = 0.024) was observed. Moreover, THA plus LSF patients showed increased incidence of mechanical complications in the first two years after THA surgery compared to THA alone patients. Conclusion This registry-based population study shows that approximately 679 (1%) THA patients were subjected to LSF. Patients undergoing THA and LSF have an increased risk of mechanical complications with their THA and a slightly increased risk of revision arthroplasty. Cite this article: Bone Joint J 2021;103-B(3):486–491.
Single dose of tranexamic acid effectively reduces blood loss and transfusion rates in elderly patients undergoing surgery for hip fracture: a randomized controlled trial
Authors: Nikolaou Vasileios S. , Masouros Panagiotis , Floros Themistoklis , Chronopoulos Efstathios , Skertsou Maria , Babis George C. 
Published: February 2021

Aims The aim of this study was to investigate the hypothesis that a single dose of tranexamic acid (TXA) would reduce blood loss and transfusion rates in elderly patients undergoing surgery for a subcapital or intertrochanteric (IT) fracture of the hip. Methods In this single-centre, randomized controlled trial, elderly patients undergoing surgery for a hip fracture, either hemiarthroplasty for a subcapital fracture or intramedullary nailing for an IT fracture, were screened for inclusion. Patients were randomly allocated to a study group using a sealed envelope. The TXA group consisted of 77 patients, (35 with a subcapital fracture and 42 with an IT fracture), and the control group consisted of 88 patients (29 with a subcapital fracture and 59 with an IT fracture). One dose of 15 mg/kg of intravenous (IV) TXA diluted in 100 ml normal saline (NS,) or one dose of IV placebo 100 ml NS were administered before the incision was made. The haemoglobin (Hb) concentration was measured before surgery and daily until the fourth postoperative day. The primary outcomes were the total blood loss and the rate of transfusion from the time of surgery to the fourth postoperative day. Results Homogeneity with respect to baseline characteristics was ensured between groups. The mean total blood loss was significantly lower in patients who received TXA (902.4 ml (-279.9 to 2,156.9) vs 1,226.3 ml (-269.7 to 3,429.7); p = 0.003), while the likelihood of requiring a transfusion of at least one unit of red blood cells was reduced by 22%. Subgroup analysis showed that these differences were larger in patients who had an IT fracture compared with those who had a subcapital fracture. Conclusion Elderly patients who undergo intramedullary nailing for an IT fracture can benefit from a single dose of 15 mg/kg TXA before the onset of surgery. A similar tendency was identified in patients undergoing hemiarthroplasty for a subcapital fracture but not to a statistically significant level. Cite this article: Bone Joint J 2021;103-B(3):442–448.
Complications, mobility, and quality of life in ankle sarcoma patients
Authors: Smolle Maria Anna , Leithner Andreas , Kapper Martin , Demmer Gregor , Trost Carmen , Bergovec Marko , Windhager Reinhard , Hobusch Gerhard Martin 
Published: February 2021

AimsThe aims of the study were to analyze differences in surgical and oncological outcomes, as well as quality of life (QoL) and function in patients with ankle sarcomas undergoing three forms of surgical treatment, minor or major limb salvage surgery (LSS), or amputation.MethodsA total of 69 patients with ankle sarcomas, treated between 1981 and 2017 at two tumour centres, were retrospectively reviewed (mean age at surgery: 46.3 years (SD 22.0); 31 females (45%)). Among these 69 patients 25 were analyzed prospectively (mean age at latest follow-up: 61.2 years (SD 20.7); 11 females (44%)), and assessed for mobility using the Prosthetic Limb Users Survey of Mobility (PLUS-M; for amputees only), the Toronto Extremity Salvage Score (TESS), and the University of California, Los Angeles (UCLA) Activity Score. Individual QoL was evaluated in these 25 patients using the five-level EuroQol five-dimension (EQ-5D-5L) and Fragebogen zur Lebenszufriedenheit/Questions on Life Satisfaction (FLZ).ResultsOf the total number of patients in the study, 22 (32%) underwent minor LSS and 22 (32%) underwent major LSS; 25 underwent primary amputation (36%). Complications developed in 26 (38%) patients, and were more common in those with major or minor LSS in comparison to amputation (59% vs 36% vs 20%; p = 0.022). A time-dependent trend towards higher complication risk following any LSS was present (relative risk: 0.204; 95% confidence interval (CI) 0.026 to 1.614; p = 0.095). In the prospective cohort, mean TESS was higher following minor LSS in comparison to amputation (91.0 vs 67.3; p = 0.006), while there was no statistically significant difference between major LSS and amputation (81.6 vs 67.3; p = 0.099). There was no difference in mean UCLA (p = 0.334) between the three groups (p = 0.334). None of the items in FLZ or EQ-5D-5L were different between the three groups (all p > 0.05), except for FLZ item “self-relation”, being lower in amputees.ConclusionComplications are common following LSS for ankle sarcomas. QoL is comparable between patients with LSS or amputation, despite better mobility scores for patients following minor LSS. We conclude that these results allow a decision for amputation to be made more easily in patients particularly where the principles of oncological surgery would otherwise be at risk. Cite this article: Bone Joint J 2021;103-B(3):553–561.
Translanguaging in writing: a bilingual PhD student’s reflection
Authors: Dong Rongrong 
Published: February 2021

AbstractWith a critical narrative approach, this reflective practice research aims to do a personal narrative inquiry on the researcher herself during her dissertation research/writing period. The researcher explores and reflects on her various translanguaging strategies used throughout the course of her dissertation research and writing. Data collection includes her reflective journal entries, interview recordings and transcriptions with her research participants, reflective conversation audio recordings with her peers and research voice memos during her dissertation writing process. Using narrative analysis, this study indicates translanguaging allows the researcher to establish her dual-identities in both U.S. and Chinese educational settings, and helps her to develop her own writer’s voice and also engages her to think more creatively and critically as a researcher and a writer. This study presents a first-person reflective practice that deconstructs bilingual PhD students’ dissertation writing journey. It highlights the significance of bilingual international graduate students’ language repertoire to their academic writing, which matters not only to individual students, but may better serve international student community cross the world.
Von der Kaminkarriere zur boundaryless und protean career? Zum Verhältnis von organisationaler und individueller Karrieresteuerung am Beispiel von Auslandseinsätzen / From organization career to boundaryless and protean career? Analysis of relations between organizational and individual career management in assignments abroad
Authors: Mense-Petermann Ursula 
Published: February 2021

Abstract
Michael Arthur und Douglas Hall haben mit ihren Thesen zur boundaryless und zur protean career eine Debatte über einen Wandel des für westliche Industriegesellschaften typischen Karrieremusters postuliert, und zwar eine Umstellung von der Organisation und des in ihr und von ihr institutionalisierten Karrieremusters der sogenannten ,Kaminkarriere’ auf den einzelnen Erwerbstätigen und seine individuellen Strukturierungs- und Selbst-Managementleistungen. Der hier vorliegende Beitrag vertritt die These, dass hier die Rolle der Organisation für Karrieren zu stark heruntergespielt und zu wenig nach dem Verhältnis von organisationalem und individuellem Karrieremanagement gefragt wird. Der Beitrag macht deshalb einen differenzierenden Vorschlag zur Analyse eines Formwandels von Karriere.
Differentialgeometrische Beschreibung und Analyse Tor-basierter Hamilton'scher Systeme
Authors: Schöberl Markus 
Published: February 2021

Zusammenfassung
In diesem Beitrag wird gezeigt, wie man ausgehend von geometrischen Strukturen, welche
man Tor-basierten Hamilton'schen Systemen im finit-dimensionalen Szenario zugrundelegen kann, durch deren Verallgemeinerung
unterschiedliche Tor-basierte Hamilton'sche Darstellungen im Rahmen partieller Differentialgleichungen gewinnt.
Diese unterschiedlichen Systemdarstellungen werden anhand eines mechanischen Beispiels, dem Timoshenko Balken, gegenübergestellt und diskutiert.
Hauptaugenmerk liegt auf der Analyse von strukturellen Eigenschaften der Differentialgleichungen, welche
dann aus regelungstechnischer Sicht von Bedeutung sind.
Flachheitsbasierte Bewegungsplanung für gekoppelte elastische Balken
Authors: Kater Andreas , Meurer Thomas 
Published: February 2021

Zusammenfassung
Dieser Beitrag stellt eine systematische Entwurfsmethodik zur flachheitsbasierten Vorsteuerung und Trajektorienplanung für gekoppelte
elastische Balkenstrukturen mit piezoelektrischen Aktoren vor. Auf Basis des mathematischen Modells wird unter Ausnutzung der
spektralen Eigenschaften ein analytischer Zugang zur Konstruktion eines flachen Ausgangs dargestellt. Dies führt auf eine
differenzielle Parametrierung sämtlicher Systemvariablen. Der Nachweis der Konvergenz macht von Eigenschaften ganzer Funktionen in
Kombination mit asymptotischen Eigenwertverteilungen Gebrauch und führt auf ein Problem der Trajektorienplanung für den flachen
Ausgang. Dieser Entwurfsansatz dient als methodische Basis für die Entwicklung eines effizienten semi-analytischen Verfahrens, das
insbesondere die Einbindung geeigneter Approximationen des verteilt-parametrischen Systems ermöglicht. Beide Ansätze werden anhand der
betrachteten Balkenstruktur analysiert und im Rahmen von Simulationen und Experimenten an einem Versuchsaufbau evaluiert.
Befähigung im Wandel
Authors: Bonte Achim 
Published: February 2021

ZusammenfassungQualifikation, Motivation und Beteiligungschancen des Personals sind der Schlüssel für den notwendigen, gründlichen Umbau der Bibliotheken im digitalen Zeitalter. Der Beitrag skizziert die besonderen Rahmenbedingungen von Personalarbeit im Öffentlichen Dienst und den aktuellen Entwicklungsstand im Bibliothekswesen, um danach die konkreten Herausforderungen für Personalgewinnung und -entwicklung näher zu betrachten. Abschließend werden beispielhaft einige Bausteine für gelungene Personalarbeit in deutschen Bibliotheken vorgestellt.1