bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment
Authors: Braun Leah T. , Rubinstein German , Zopp Stephanie , Vogel Frederick , Schmid-Tannwald Christine , Escudero Montserrat Pazos , Honegger Jürgen , Ladurner Roland , Reincke Martin 
Published: August 2020

Abstract
Purpose
Recurrence after pituitary surgery in Cushing’s disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD.

Methods
We systematically screened the literature regarding recurrent and persistent Cushing’s disease using the MESH term Cushing’s disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review.

Results and conclusions
Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.
A Novel Interaction of Translocator Protein 18 kDa (TSPO) with NADPH Oxidase in Microglia
Authors: Loth Meredith K. , Guariglia Sara R. , Re Diane B. , Perez Juan , de Paiva Vanessa Nunes , Dziedzic Jennifer L. , Chambers Jeremy W. , Azzam Diana J. , Guilarte Tomás R. 
Published: August 2020

AbstractIn the brain neuropil, translocator protein 18 kDa (TSPO) is a stress response protein that is upregulated in microglia and astrocytes in diverse central nervous system pathologies. TSPO is widely used as a biomarker of neuroinflammation in preclinical and clinical neuroimaging studies. However, there is a paucity of knowledge on the function(s) of TSPO in glial cells. In this study, we explored a putative interaction between TSPO and NADPH oxidase 2 (NOX2) in microglia. We found that TSPO associates with gp91phox and p22phox, the principal subunits of NOX2 in primary murine microglia. The association of TSPO with gp91phox and p22phox was observed using co-immunoprecipitation, confocal immunofluorescence imaging, and proximity ligation assay. We found that besides gp91phox and p22phox, voltage-dependent anion channel (VDAC) also co-immunoprecipitated with TSPO consistent with previous reports. When we compared lipopolysaccharide (LPS) stimulated microglia to vehicle control, we found that a lower amount of gp91phox and p22phox protein co-immunoprecipitated with TSPO suggesting a disruption of the TSPO-NOX2 subunits association. TSPO immuno-gold electron microscopy confirmed that TSPO is present in the outer mitochondrial membrane but it is also found in the endoplasmic reticulum (ER), mitochondria-associated ER membrane (MAM), and in the plasma membrane. TSPO localization at the MAM may represent a subcellular site where TSPO interacts with gp91phox and p22phox since the MAM is a point of communication between outer mitochondria membrane proteins (TSPO) and ER proteins (gp91phox and p22phox) where they mature and form the cytochrome b558 (Cytb558) heterodimer. We also found that an acute burst of reactive oxygen species (ROS) increased TSPO levels on the surface of microglia and this effect was abrogated by a ROS scavenger. These results suggest that ROS production may alter the subcellular distribution of TSPO. Collectively, our findings suggest that in microglia, TSPO is associated with the major NOX2 subunits gp91phox and p22phox. We hypothesize that this interaction may regulate Cytb558 formation and modulate NOX2 levels, ROS production, and redox homeostasis in microglia.
The N-acyl homoserine-lactone depleted Rhizobium radiobacter mutant RrF4NM13 shows reduced growth-promoting and resistance-inducing activities in mono- and dicotyledonous plants
Authors: Alabid Ibrahim , Hardt Martin , Imani Jafargholi , Hartmann Anton , Rothballer Michael , Li Dan , Uhl Jenny , Schmitt-Kopplin Philippe , Glaeser Stefanie , Kogel Karl-Heinz 
Published: August 2020

AbstractThe Alphaproteobacterium Rhizobium radiobacter (syn. Agrobacterium tumefaciens, “A. fa brum”) can live in close association with the sebacinoid fungus Serendipita (syn. Piriformospora) indica that forms a mutualistic Sebacinalean symbiosis with a wide range of host plants. The endobacterial strain R. radiobacter F4 (RrF4), which was originally isolated from the fungus, has plant growth promotion and resistance-inducing activities resembling the beneficial activities known from the endobacteria-containing S. indica. The mechanism by which free endobacterial cells influence growth and disease resistance of colonized host plants is not fully understood. Here, we show that RrF4 produces a spectrum of quorum sensing-mediating N-acyl-homoserine lactones (AHLs) with acyl chains of C8, C10, and C12 as well as hydroxyl- or oxo-substitutions at the C3 position. In addition, and in line with previous findings showing that AHLs increase plant biomass and induce systemic resistance, the AHL-depleted lactonase-overexpressing transconjugant RrF4NM13 was partially compromised in promoting growth and inducing resistance against bacterial pathogens in both Arabidopsis thaliana and wheat (Triticum aestivum). Scanning and transmission electron microscopy proved that RrF4NM13, in contrast to RrF4, does not form cellulose-like fiber scaffolds for efficient root surface attachment. Moreover, RrF4NM13 does not penetrate into the intercellular space of the cortical tissue, which in contrast is strongly colonized by RrF4. We discuss the possibility that AHLs contribute to the outcome of the Sebacinalean symbiosis.
Reputation systems and recruitment in online labor markets: insights from an agent-based model
Authors: Lukac Martin , Grow André 
Published: August 2020

AbstractOnline labor markets—freelance marketplaces, where digital labor is distributed via a web-based platform—commonly use reputation systems to overcome uncertainties in the hiring process, that can arise from a lack of objective information about employees’ abilities. Research shows, however, that reputation systems tend to create winner-takes-all dynamics, in which differences in candidates’ reputations become disconnected from differences in their objective abilities. In this paper, we use an empirically validated agent-based computational model to investigate the extent to which reputation systems can create segmented hiring patterns that are biased toward freelancers with good reputation. We explore how jobs and earnings become distributed on a stylized platform, under different contextual conditions of information asymmetry. Our results suggest that information asymmetry influences the extent to which reputation systems may lead to inequality between freelancers, but contrary to our expectations, lower levels of information asymmetry can facilitate higher inequality in outcomes.
Observing System Impact on Ionospheric Specification Over China Using EnKF Assimilation
Authors: He Jianhui , Yue Xinan , Hu Lianhuan , Wang Junyi , Li Mingyuan , Ning Baiqi , Wan Weixing , Xu Jiyao 
Published: August 2020

AbstractAccurate ionospheric specification for the current and future is one of the key tasks in operational space weather. In this work, we have assessed the effect of a dense ground network consisting of different radio instruments either developed or under developing on ionosphere nowcasting and forecasting over China and adjacent region (0–60°N and 70–140°E) through observing system simulation experiments. The data assimilation system is an Ensemble Kalman filter (EnKF) ionosphere and thermosphere data assimilation algorithm. The National Center for Atmospheric Research Thermosphere Ionosphere Electrodynamics General Circulation Model is used as a background model. Effects of different observation types, including the slant total electron content from Beidou System geostationary satellite and Global Position System and electron density observations from ionosondes and incoherent scattering radar on the ionospheric nowcasting and forecasting, are examined by the accurate specification of ionosphere key parameters (total electron content and 3‐D electron density). We found that simultaneously assimilating different observation types can greatly improve the quality of ionosphere specification. Furthermore, updating the thermospheric state variables in the coupled thermosphere‐ionosphere forecast model in the assimilation step plays an important role in improving the ionosphere forecasting. The ionosphere forecasting capability can last longer (>24 hr) in each observing system simulation experiment due to the adjusted thermosphere states. This study can provide a reference for observing system design over the China region and future ionosphere forecasting operation.
Phase 1/2a trial of intravenous BAL101553, a novel controller of the spindle assembly checkpoint, in advanced solid tumours
Authors: Kristeleit Rebecca , Evans Jeffry , Molife L. Rhoda , Tunariu Nina , Shaw Heather , Slater Sarah , Haris Noor R. Md , Brown Nicholas F. , Forster Martin D. , Diamantis Nikolaos , Rulach Robert , Greystoke Alastair , Asghar Uzma , Rata Mihaela , Anderson Stephanie , Bachmann Felix , Hannah Alison , Kaindl Thomas , Lane Heidi A. , Larger Patrice J. , Schmitt-Hoffmann Anne , Engelhardt Marc , Tzankov Alexandar , Plummer Ruth , Lopez Juanita 
Published: August 2020

AbstractBackgroundBAL101553 (lisavanbulin), the lysine prodrug of BAL27862 (avanbulin), exhibits broad anti-proliferative activity in human cancer models refractory to clinically relevant microtubule-targeting agents.MethodsThis two-part, open-label, phase 1/2a study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of 2-h infusion of BAL101553 in adults with advanced or recurrent solid tumours. The MTD was determined using a modified accelerated titration design in phase I. Patients received BAL101553 at the MTD and at lower doses in the phase 2a expansion to characterise safety and efficacy and to determine the recommended phase 2 dose (RP2D).ResultsSeventy-three patients received BAL101553 at doses of 15–80 mg/m2(phase 1,n = 24; phase 2a,n = 49). The MTD was 60 mg/m2; DLTs observed at doses ≥60 mg/m2were reversible Grade 2–3 gait disturbance with Grade 2 peripheral sensory neuropathy. In phase 2a, asymptomatic myocardial injury was observed at doses ≥45 mg/m2. The RP2D for 2-h intravenous infusion was 30 mg/m2. The overall disease control rate was 26.3% in the efficacy population.ConclusionsThe RP2D for 2-h infusion of BAL101553 was well tolerated. Dose-limiting neurological and myocardial side effects were consistent with the agent’s vascular-disrupting properties.Clinical trial registrationEudraCT: 2010-024237-23.
First-in-human, dose-escalation, phase 1 study of anti-angiopoietin-2 LY3127804 as monotherapy and in combination with ramucirumab in patients with advanced solid tumours
Authors: Martin-Liberal Juan , Hollebecque Antoine , Aftimos Philippe , Jungels Christiane , Martin-Romano Patricia , Rodon Jordi , Kremer Jill Dolores , Zhang Wei , Bendell Johanna 
Published: August 2020

Abstract
Background
This is the first-in-human study of novel anti-angiopoietin-2 (Ang-2) monoclonal antibody LY3127804 as monotherapy and in combination with ramucirumab in advanced solid tumours.

Methods
Patients received intravenous LY3127804 monotherapy (4, 8, 12, 16, 20 and 27 mg/kg) in part A; LY3127804 (8, 12, 16, 20 and 27 mg/kg) with 8 mg/kg ramucirumab in part B; and LY3127804 (20 mg/kg) with 12 mg/kg ramucirumab in part C. Treatments were administered every 2 weeks (Q2W) during 28-day cycles. Dose-escalation was based on cycle 1 dose-limiting toxicities (DLTs).

Results
Sixty-two patients were treated in part A (n = 20), part B (n = 35) and part C (n = 7). Constipation, diarrhoea and fatigue were the most common treatment-emergent adverse events (TEAEs) in part A; hypertension and peripheral oedema were the most frequent TEAE in parts B and C. No DLT was observed and maximum tolerated dose for LY3127804 was not reached. Four patients achieved partial response with combination therapy (clear cell endometrial carcinoma, cervix squamous cell carcinoma, carcinoma of unknown primary and gastroesophageal junction carcinoma), 29 achieved stable disease, and 24 had progressive disease.

Conclusions
LY3127804 monotherapy and its combination with ramucirumab are well tolerated. LY3127804 20 mg/kg was the recommended Phase 2 dose.
Complete loss of ATM function augments replication catastrophe induced by ATR inhibition and gemcitabine in pancreatic cancer models
Authors: Dunlop Charles R. , Wallez Yann , Johnson Timothy Isaac , Bernaldo de Quirós Fernández Sandra , Durant Stephen T. , Cadogan Elaine B. , Lau Alan , Richards Frances M. , Jodrell Duncan I. 
Published: August 2020

AbstractBackgroundPersonalised medicine strategies may improve outcomes in pancreatic ductal adenocarcinoma (PDAC), but validation of predictive biomarkers is required. Having developed a clinical trial to assess the ATR inhibitor, AZD6738, in combination with gemcitabine (ATRi/gem), we investigated ATM loss as a predictive biomarker of response to ATRi/gem in PDAC.MethodsThrough kinase inhibition, siRNA depletion and CRISPR knockout of ATM, we assessed how ATM targeting affected the sensitivity of PDAC cells to ATRi/gem. Using flow cytometry, immunofluorescence and immunoblotting, we investigated how ATRi/gem synergise in ATM-proficient and ATM-deficient cells, before assessing the impact of ATM loss on ATRi/gem sensitivity in vivo.ResultsComplete loss of ATM function (through pharmacological inhibition or CRISPR knockout), but not siRNA depletion, sensitised to ATRi/gem. In ATM-deficient cells, ATRi/gem-induced replication catastrophe was augmented, while phospho-Chk2-T68 and phospho-KAP1-S824 persisted via DNA-PK activity. ATRi/gem caused growth delay in ATM-WT xenografts in NSG mice and induced regression in ATM-KO xenografts.ConclusionsATM loss augments replication catastrophe-mediated cell death induced by ATRi/gem and may predict clinical responsiveness to this combination. ATM status should be carefully assessed in tumours from patients with PDAC, since distinction between ATM-low and ATM-null could be critical in maximising the success of clinical trials using ATM expression as a predictive biomarker.
Clinical Presentation of Chronic Traumatic Encephalopathy
Authors: Mariani Megan , Alosco Michael L. , Mez Jesse , Stern Robert A. 
Published: August 2020

AbstractChronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impacts (RHI), such as those received in contact/collision sports, blast injury in military veterans, and domestic violence. Currently, CTE can only be diagnosed following death. Although the clinical features of former boxers have been described for almost a century, and there is increasing evidence of long-term cognitive and neuropsychiatric impairments in living former American football players, the specific clinical presentation associated with underlying CTE neuropathology remains unclear. These features include diverse and nonspecific changes in cognition, mood, behavior, and motor functioning. Currently, there are no validated and widely accepted clinical diagnostic criteria. Proposed criteria are primarily based on retrospective telephonic interviews with the next of kin of individuals who were diagnosed with CTE postmortem. Prospective studies involving individuals presumably at high risk for CTE are underway; these will hopefully clarify the clinical features and course of CTE, allow the diagnostic criteria to be refined, and lead to the development and validation of in vivo biomarkers. This article reviews what is currently known about the clinical presentation of CTE and describes the evolution of this knowledge from early case reports of “punch drunk” boxers through larger case series of neuropathologically confirmed CTE. This article concludes with a discussion of gaps in research and future directions to address these areas.
Fluid Biomarkers for Chronic Traumatic Encephalopathy
Authors: Shahim Pashtun , Gill Jessica M. , Blennow Kaj , Zetterberg Henrik 
Published: August 2020

AbstractChronic traumatic encephalopathy (CTE) is a neuropathological condition that has been described in individuals who have been exposed to repetitive head impacts, including concussions and subconcussive trauma. Currently, there is no fluid or imaging biomarker for diagnosing CTE during life. Based on retrospective clinical data, symptoms of CTE include changes in behavior, cognition, and mood, and may develop after a latency phase following the injuries. However, these symptoms are often nonspecific, making differential diagnosis based solely on clinical symptoms unreliable. Thus, objective biomarkers for CTE pathophysiology would be helpful in understanding the course of the disease as well as in the development of preventive and therapeutic measures. Herein, we review the literature regarding fluid biomarkers for repetitive concussive and subconcussive head trauma, postconcussive syndrome, as well as potential candidate biomarkers for CTE. We also discuss technical challenges with regard to the current fluid biomarkers and potential pathways to advance the most promising biomarker candidates into clinical routine.
Measuring the usability of machine translation in the classroom context
Authors: Yang Yanxia , Wang Xiangling , Yuan Qingqing 
Published: August 2020

Abstract
Usability is a key factor for increasing adoption of machine translation. This study aims to measure the usability
of machine translation in the classroom context by comparing translation students’ machine translation post-editing output with
their manual translation in two comparable translation tasks. Three dimensions of usability were empirically measured:
efficiency, effectiveness, and satisfaction. The findings suggest that machine translation
post-editing is more efficient than human translation and post-editing produces fewer errors than human translation. While the
types of errors vary, errors in terms of accuracy outnumber those related to fluency. In addition, participants perceive the
amount of time and work that is saved when post-editing to be greater benefit than the overall utility of post-editing. Likewise,
students report a strong desire to learn post-editing skills in training programs.
Characterization of collagenase found in the nonpathogenic bacterium Lysinibacillus sphaericus VN3
Authors: Hoa Bach Thi Mai , Pham Thanh Huyen , Dinh Truong Son , Takagi Hiroshi 
Published: August 2020

Abstract
High collagenolytic activity has been detected in pathogenic bacteria. Collagenase plays an essential role in the invasion step in animals and humans. In this study, we characterized collagenase found in the nonpathogenic bacterium Lysinibacillus sphaericus VN3, which was isolated from soil in Vietnam. The collagenase activity of the purified enzyme was strongly inhibited by Cu2+, but it was significantly increased by Zn2+. The purified enzyme with a molecular mass of approximately 110 kDa exhibited collagenolytic, gelatinolytic, and caseinolytic activity. The kinetic studies showed that this enzyme had greater hydrolyzing activity toward collagen and gelatin compared with casein. Based on the ratio Vmax/Km, collagen is likely to be the best substrate among three proteins. We found that this collagenase could digest small pieces of bovine skin and tendon into a collagen solution. Interestingly, at pH 6.0–8.0, the soluble collagen could form a collagen membrane, which is useful as a wound-healing biomaterial.
Nested Variant of Urothelial Carcinoma Is a Luminal Bladder Tumor With Distinct Coexpression of the Basal Marker Cytokeratin 5/6
Authors: Johnson Steven M , Khararjian Armen , Legesse Teklu B , Khani Francesca , Robinson Brian D , Epstein Jonathan I , Wobker Sara E 
Published: August 2020

Abstract

Objectives
The nested variant of urothelial carcinoma (NVUC) is a rare bladder tumor that may possess a luminal molecular phenotype. We sought to determine whether a small immunohistochemical (IHC) panel using common surrogates for molecular phenotypes would reliably classify a cohort of pure NVUC cases.

Methods
IHC staining with a panel composed of markers for basal subtypes (CK5/6, CK14) and luminal subtypes (FOXA1, GATA3) was performed on pure small NVUC cases (n = 23) and 5 large NVUC cases (n = 5). Scoring of IHC stains was performed semiquantitatively. Individual cases were analyzed using previously reported IHC-based surrogates for molecular subtype.

Results
The phenotype of NVUC was classified as luminal from 60.1% (FOXA1+/CK5/6−) to 100% (GATA3+/CK14−) of cases using composite phenotypes. No cases possessed a basal or squamous cell carcinoma–like phenotype. The majority of small NVUC cases (69.5%) showed subset CK5/6 expression distinctly localized to the basal layers of tumor cell nests. Intratumoral heterogeneity was also noted in CK5/6 (21.7% of small NVUC cases) but no other markers.

Conclusions
NVUC appears to express markers of both basal and luminal bladder tumors. Definitive gene expression profiling may be valuable to further characterize this unique histologic variant.
Variations in genetic structure and male genitalia suggest recent lineage diversification in the Neotropical dung beetle complexCanthon cyanellus(Scarabaeidae: Scarabaeinae)
Authors: Nolasco-Soto Janet , Favila Mario E , Espinosa De Los Monteros Alejandro , González-Astorga Jorge , Halffter Gonzalo , Valdez-Carrasco Jorge , Noriega Jorge Ari , Galante Eduardo 
Published: August 2020

AbstractWe analysed the genetic divergence and morphology of the aedeagus (i.e. phallobase and parameres) in Canthon cyanellus at different geographical levels. The results from both approaches were compared with the current taxonomic assignment of the C. cyanellus complex, which includes three subspecies. We found a high variation in all the morphological characters of the aedeagus in the populations analysed; the morphometric variation was not geographically structured, either by population or by region. The genealogical analysis indicates a significant genetic structure that does not match either the morphological variation in the male genitalia or the previous subspecific taxonomic classification. Our results suggest that the morphological variation of the aedeagus is seemingly not an isolating reproductive barrier and that the intra- and interpopulation morphological variability of the aedeagus in the C. cyanellus complex does not permit the division into several species. We suggest that other evolutionary forces, such as genetic drift and sexual selection, have influenced the evolution of the male genitalia and the incipient differentiation of this species complex.